Science.gov

Sample records for brittle bone disease

  1. Children with Brittle Bones.

    ERIC Educational Resources Information Center

    Alston, Jean

    1982-01-01

    Special help given to children with Osteogenesis Imperfecta (brittle bone disease) is described, including adapted equipment to allow for writing and use of a classroom assistant to aid participation in a regular classroom. (CL)

  2. Johanna and Tommy: Two Preschoolers in Sweden with Brittle Bones.

    ERIC Educational Resources Information Center

    Millde, Kristina; Brodin, Jane

    Information is presented for caregivers of Swedish children with osteogenesis imperfecta (brittle bones) and their families. Approximately five children with brittle bones are born in Sweden annually. Two main types of brittle bone disease have been identified: congenita and tarda. Typical symptoms include numerous and unexpected fractures, bluish…

  3. Battling Brittle Bones

    NASA Technical Reports Server (NTRS)

    2002-01-01

    The accuDEXA(R) Bone Mineral Density Assessment System, manufactured by Schick Technologies, Inc., utilizes "camera on a chip" sensor technology invented and developed by NASA's Jet Propulsion Laboratory. Schick's accuDEXA system offers several advantages over traditional osteoporosis tests, which assess bone density loss in the hip and spine, and require specialized personnel to conduct. With accuDEXA, physicians can test the entire body's bone density at a peripheral site, such as the finger, without applying gels or having patients remove garments. Results are achieved in 30 seconds and printed out in less than a minute, compared to the estimated exam time of 15 minutes for hip and spine density analyses. Schick has also applied the CMOS APS technology to a new software product that performs dental radiography using up to 90 percent less radiation exposure than conventional X-rays. Called Computed Dental Radiography(R), the new digital imaging product utilizes an electronic sensor in place of X-ray film to generate sharp and clear images that appear on a computer screen within 3 seconds, and can be enlarged and enhanced to identify problems.

  4. Preventing and Treating Brittle Bones and Osteoporosis | NIH MedlinePlus the Magazine

    MedlinePlus

    ... Javascript on. Feature: Osteoporosis Preventing and Treating Brittle Bones and Osteoporosis Past Issues / Winter 2011 Table of ... at high risk due to low bone mass. Bone and Bone Loss Bone is living, growing tissue. ...

  5. Children with Brittle Bones: An Examination of Their Educational Needs and Progress.

    ERIC Educational Resources Information Center

    Alston, Jean

    1983-01-01

    A study of the educational achievements of 40 children (5-16 years old) with osteogenesis imperfecta, brittle bone disease, revealed no differences between Ss and control Ss without the condition in terms of nonverbal intelligence. Differences were found, however, in writing speed. Inteviews with children, teachers, and parents revealed…

  6. From brittle to ductile fracture of bone

    NASA Astrophysics Data System (ADS)

    Peterlik, Herwig; Roschger, Paul; Klaushofer, Klaus; Fratzl, Peter

    2006-01-01

    Toughness is crucial to the structural function of bone. Usually, the toughness of a material is not just determined by its composition, but by the ability of its microstructure to dissipate deformation energy without propagation of the crack. Polymers are often able to dissipate energy by viscoplastic flow or the formation of non-connected microcracks. In ceramics, well-known toughening mechanisms are based on crack ligament bridging and crack deflection. Interestingly, all these phenomena were identified in bone, which is a composite of a fibrous polymer (collagen) and ceramic nanoparticles (carbonated hydroxyapatite). Here, we use controlled crack-extension experiments to explain the influence of fibre orientation on steering the various toughening mechanisms. We find that the fracture energy changes by two orders of magnitude depending on the collagen orientation, and the angle between collagen and crack propagation direction is decisive in switching between different toughening mechanisms.

  7. From brittle to ductile fracture of bone.

    PubMed

    Peterlik, Herwig; Roschger, Paul; Klaushofer, Klaus; Fratzl, Peter

    2006-01-01

    Toughness is crucial to the structural function of bone. Usually, the toughness of a material is not just determined by its composition, but by the ability of its microstructure to dissipate deformation energy without propagation of the crack. Polymers are often able to dissipate energy by viscoplastic flow or the formation of non-connected microcracks. In ceramics, well-known toughening mechanisms are based on crack ligament bridging and crack deflection. Interestingly, all these phenomena were identified in bone, which is a composite of a fibrous polymer (collagen) and ceramic nanoparticles (carbonated hydroxyapatite). Here, we use controlled crack-extension experiments to explain the influence of fibre orientation on steering the various toughening mechanisms. We find that the fracture energy changes by two orders of magnitude depending on the collagen orientation, and the angle between collagen and crack propagation direction is decisive in switching between different toughening mechanisms.

  8. How tough is Brittle Bone? Investigating Osteogenesis Imperfecta in Mouse Bone††

    PubMed Central

    Carriero, A.; Zimmermann, E. A.; Paluszny, A.; Tang, S. Y.; Bale, H.; Busse, B.; Alliston, T.; Kazakia, G.

    2015-01-01

    The multiscale hierarchical structure of bone is naturally optimized to resist fractures. In osteogenesis imperfecta, or brittle bone disease, genetic mutations affect the quality and/or quantity of collagen, dramatically increasing bone fracture risk. Here we reveal how the collagen defect results in bone fragility in a mouse model of osteogenesis imperfecta (oim), which has homotrimeric α1(I) collagen. At the molecular level we attribute the loss in toughness to a decrease in the stabilizing enzymatic crosslinks and an increase in non-enzymatic crosslinks, which may break prematurely inhibiting plasticity. At the tissue level, high vascular canal density reduces the stable crack growth, and extensive woven bone limits the crack-deflection toughening during crack growth. This demonstrates how modifications at the bone molecular level have ramifications at larger length scales affecting the overall mechanical integrity of the bone; thus, treatment strategies have to address multiscale properties in order to regain bone toughness. In this regard, findings from the heterozygous oim bone, where defective as well as normal collagen are present, suggest that increasing the quantity of healthy collagen in these bones helps to recover toughness at the multiple length scales. PMID:24420672

  9. [Bone diseases].

    PubMed

    Uebelhart, Brigitte; Rizzoli, René

    2016-01-13

    Calcium intake shows a small impact on bone mineral density and fracture risk. Denosumab is a more potent inhibitor of bone resorption than zoledronate. Abaloparatide, PTHrP analog, increases bone mineral density and decreases fracture incidence. Teriparatide could be delivered via a transdermic device. Romosozumab and odanacatib improve calculated bone strength. Sequential or combined treatments with denosumab and teriparatide could be of interest, but not denosumab followed by teriparatide. Fibrous dysplasia, Paget disease and hypophosphatasia are updated, as well as atypical femoral fracture and osteonecrosis of the jaw.

  10. Paget's Disease of Bone

    MedlinePlus

    ... page please turn Javascript on. Paget's Disease of Bone What is Paget's Disease of Bone? Click for more information Enlarged and Misshapen Bones Paget's disease of bone causes affected bones to ...

  11. Bone Diseases

    MedlinePlus

    Your bones help you move, give you shape and support your body. They are living tissues that rebuild constantly ... childhood and your teens, your body adds new bone faster than it removes old bone. After about ...

  12. AN INVESTIGATION OF THE MINERAL IN DUCTILE AND BRITTLE CORTICAL MOUSE BONE

    PubMed Central

    Rodriguez-Florez, Naiara; Garcia-Tunon, Esther; Mukadam, Quresh; Saiz, Eduardo; Oldknow, Karla J.; Farquharson, Colin; Millán, José Luis; Boyde, Alan; Shefelbine, Sandra J.

    2015-01-01

    Bone is a strong and tough material composed of apatite mineral, organic matter and water. Changes in composition and organization of these building blocks affect bone’s mechanical integrity. Skeletal disorders often affect bone’s mineral phase, either by variations in the collagen or directly altering mineralization. The aim of the current study was to explore the differences in the mineral of brittle and ductile cortical bone at the mineral (nm) and tissue (µm) levels using two mouse phenotypes. Osteogenesis imperfecta murine (oim−/−) mice were used to model brittle bone; PHOSPHO1 mutants (Phospho1−/−) had ductile bone. They were compared to their respective wild-type controls. Femora were defatted and ground to powder to measure average mineral crystal size using X-ray diffraction (XRD), and to monitor the bulk mineral to matrix ratio via thermogravimetric analysis (TGA). XRD scans were run after TGA for phase identification, to assess the fractions of hydroxyapatite and β-tricalcium phosphate. Tibiae were embedded to measure elastic properties with nanoindentation and the extent of mineralization with backscattered electron microscopy (qbSEM). Interestingly, the mineral of brittle oim−/− and ductile Phospho1−/− bones had many similar characteristics. Both pathology models had smaller apatite crystals, lower mineral to matrix ratio, and showed more thermal conversion to β-tricalcium phosphate than their wild-types, indicating deviations from stoichiometric hydroxyapatite in the original mineral. The degree of mineralization of the bone matrix was different for each strain: oim−/− were hypermineralized, while Phospho1−/− were hypomineralized. However, alterations in the mineral were associated with reduced tissue elastic moduli in both pathologies. Results revealed that despite having extremely different whole bone mechanics, the mineral of oim−/− and Phospho1−/− has several similar trends at smaller length scales. This

  13. Bone Marrow Diseases

    MedlinePlus

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

  14. Metastatic Bone Disease

    MedlinePlus

    ... secrete factors that interact with the naturally occurring cells in the bone and cause bone destruction, new bone formation, or both. Effects Because MBD weakens the affected bones, people with the disease are prone to fractures. Broken ...

  15. Thrombospondin-2 deficiency in growing mice alters bone collagen ultrastructure and leads to a brittle bone phenotype

    PubMed Central

    Manley, Eugene; Perosky, Joseph E.; Khoury, Basma M.; Reddy, Anita B.; Kozloff, Kenneth M.

    2015-01-01

    Thrombospondin-2 (TSP2) is a matricellular protein component of the bone extracellular matrix. Long bones of adult TSP2-deficient mice have increased endosteal bone thickness due to expansion of the osteoblast progenitor cell pool, and these cells display deficits in osteoblastic potential. Here, we investigated the effects of TSP2 deficiency on whole bone geometric and mechanical properties in growing 6-wk-old male and female wild-type and TSP2-knockout (KO) mice. Microcomputed tomography and mechanical testing were conducted on femora and L2 vertebrae to assess morphology and whole bone mechanical properties. In a second series of experiments, femoral diaphyses were harvested from wild-type and TSP2-KO mice. Detergent-soluble type I collagen content was determined by Western blot of right femora. Total collagen content was determined by hydroxyproline analysis of left femora. In a third series of experiments, cortical bone was dissected from the anterior and posterior aspects of the femoral middiaphysis and imaged by transmission electron microscopy to visualize collagen fibrils. Microcomputed tomography revealed minimal structural effects of TSP2 deficiency. TSP2 deficiency imparted a brittle phenotype on cortical bone. Femoral tissue mineral density was not affected by TSP2 deficiency. Instead, transmission electron microscopy revealed less intensely stained collagen fibrils with altered morphology in the extracellular matrix assembled by osteoblasts on the anterior surface of TSP2-KO femora. Femoral diaphyseal bone displayed comparable amounts of total collagen, but the TSP2-KO bones had higher levels of detergent-extractable type I collagen. Together, our data suggest that TSP2 is required for optimal collagen fibrillogenesis in bone and thereby contributes to normal skeletal tissue quality. PMID:26272319

  16. Autoinflammatory bone diseases.

    PubMed

    Stern, Sara M; Ferguson, Polly J

    2013-11-01

    Autoinflammatory bone disease is a new branch of autoinflammatory diseases caused by seemingly unprovoked activation of the innate immune system leading to an osseous inflammatory process. The inflammatory bone lesions in these disorders are characterized by chronic inflammation that is typically culture negative with no demonstrable organism on histopathology. The most common autoinflammatory bone diseases in childhood include chronic nonbacterial osteomyelitis (CNO), synovitis, acne, pustulosis, hyperostosis, osteitis syndrome, Majeed syndrome, deficiency of interleukin-1 receptor antagonist, and cherubism. In this article, the authors focus on CNO and summarize the distinct genetic autoinflammatory bone syndromes.

  17. Bone scan in metabolic bone diseases. Review.

    PubMed

    Abdelrazek, Saeid; Szumowski, Piotr; Rogowski, Franciszek; Kociura-Sawicka, Agnieszka; Mojsak, Małgorzata; Szorc, Małgorzata

    2012-08-25

    Metabolic bone disease encompasses a number of disorders that tend to present a generalized involvement of the whole skeleton. The disorders are mostly related to increased bone turnover and increased uptake of radiolabelled diphosphonate. Skeletal uptake of 99mTc-labelled diphosphonate depends primarily upon osteoblastic activity, and to a lesser extent, skeletal vascularity. A bone scan image therefore presents a functional display of total skeletal metabolism and has valuable role to play in the assessment of patients with metabolic bone disorders. However, the bone scan appearances in metabolic bone disease are often non-specific, and their recognition depends on increased tracer uptake throughout the whole skeleton. It is the presence of local lesions, as in metastatic disease, that makes a bone scan appearance obviously abnormal. In the early stages, there will be difficulty in evaluating the bone scans from many patients with metabolic bone disease. However, in the more severe cases scan appearances can be quite striking and virtually diagnostic.

  18. [Bone disease in Gaucher's disease].

    PubMed

    Roca Espiau, Mercedes

    2011-09-01

    The exposition aims, is to review the pathophysiological mechanisms of bone marrow involvement and the patterns of marrow infiltration by Gaucher cells. We have reviewed the different methods of assessment of bone marrow infiltration and its temporal development. Qualitative methods include simple radiography, magnetic resonance imaging (MRI), computed tomography (CT) and radioisotope. The simple radiography is the basic element, but its sensitivity is limited and only allows for assessing changes and trabecular bone remodeling MRI allows us to appreciate the bone marrow infiltration, detection of complications and response to therapy. Radioisotopes can contribute to the differential diagnosis of osteomyelitis and bone crises. Among the quantitative methods are the QCSI (quantitative chemical shift imaging) and the dual-energy X-ray absorptiometry (DEXA), as well as new quantitative techniques of CT, MRI and ultrasound densitometry. The QCSI performed an assessment of fat content of bone marrow in the spine. DEXA quantifies bone density by measuring the attenuation coefficient. The semiquantitative methods have various "scores" to establish criteria for generalized bone disease endpoints of disease progression and response to therapy.

  19. [Metabolic bone diseases].

    PubMed

    Jakob, F

    2007-10-01

    Osteomalacia is caused by impaired vitamin D receptor (VDR) signaling, calcium deficiency, and altered bone mineralization. This can be due to insufficient sunlight exposure, malabsorption, reduced D hormone activation in chronic kidney disease, and rare alterations of VDR signaling and phosphate metabolism. Leading symptoms are bone pain, muscular cramps, and increased incidence of falls in the elderly. The adequate respective countermeasures are to optimize the daily intake of calcium and vitamin D3 and to replace active D hormone and phosphate if deficient. Osteoporosis is characterized by bone fragility fractures upon minor physical impact. Indications for diagnosis and treatment can be established by estimating the absolute fracture risk, taking into account bone mineral density, age, gender, and individual risk factors. Exercise, intervention programs to avoid falls, and specific drugs are capable of substantially reducing fracture risk even in the elderly. Secondary osteoporosis primarily requires both bone-altering medications and effective treatment of underlying diseases.

  20. Bone and Celiac Disease.

    PubMed

    Zanchetta, María Belén; Longobardi, Vanesa; Bai, Julio César

    2016-04-01

    More than 50% of untreated patients with celiac disease (CD) have bone loss detected by bone densitometry (dual-energy X-ray absorptiometry:DXA). Moreover, patients with CD are more likely to have osteoporosis and fragility fractures, especially of the distal radius. Although still controversial, we recommend DXA screening in all celiac disease patients, particularly in those with symptomatic CD at diagnosis and in those who present risk factors for fracture such as older age, menopausal status, previous fracture history, and familial hip fracture history. Bone microarchitecture, especially the trabecular network, may be deteriorated, explaining the higher fracture risk in these patients. Adequate calcium and vitamin D supplementation are also recommended to optimize bone recovery, especially during the first years of gluten free diet (GFD). If higher fracture risk persists after 1 or 2 years of GFD, specific osteoactive treatment may be necessary to improve bone health.

  1. Paget disease of the bone

    MedlinePlus

    ... that may indicate Paget disease include: Bone scan Bone x-ray Elevated markers of bone breakdown (for example, N-telopeptide) This disease may ... of Paget disease. Alternative Names Osteitis deformans Images ... X-ray References Ralston SH. Paget disease of bone. In: Goldman L, Schafer AI, eds. Goldman's Cecil ...

  2. 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.

  3. Paget Disease of Bone.

    PubMed

    Al-Rashid, Mamun; Ramkumar, Dipak B; Raskin, Kevin; Schwab, Joseph; Hornicek, Francis J; Lozano-Calderón, Santiago A

    2015-10-01

    The current understanding of Paget disease of bone (PDB) has vastly changed since Paget described the first case in 1877. Medical management of this condition remains the mainstay of treatment. Surgical intervention is usually only used in fractures through pagetic bone, need for realignment to correct deformity in major long bones, prophylactic treatment of impending fractures, joint arthroplasty in severe arthritis, or spinal decompression in cases of bony compression of neural elements. Advances in surgical technique have allowed early return to function and mobilization. Despite medical and surgical intervention, a small subset of patients with PDB develops Paget sarcoma.

  4. 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.

  5. [Infectious bone diseases].

    PubMed

    Tiemann, A H; Krenn, V; Krukemeyer, M G; Seyfert, C; Jakobs, M; Baumhoer, D; Hofmann, G O

    2011-05-01

    Bacterial infection of the bone is a severe disease with complications, potentially including long-term physical disability. The diagnosis and therapy of osteomyelitis include several elements: histopathology, microbiology, radiologic imagining, as well as antibiotic and surgical therapy. Histopathologists differentiate between acute osteomyelitis (infiltration of cancellous bone with neutrophil granulocytes); specific osteomyelitis (epithelioid-like granulomatous inflammation, tuberculosis, mycotic infections); primary/secondary chronic osteomyelitis (lymphocytic infiltration); and special forms of chronic osteomyelitis (varying histomorphology, Brodie abscess, SAPHO syndrome). Another important task in the histopathological diagnosis of inflammatory bone diseases is to differentiate osteomyelitis from malignant entities (sarcoma, lymphoma). Therefore, biopsy samples should be of sufficient size for safe diagnosis. Clinical information and imaging as well as interdisciplinary teamwork between radiologists, microbiologists, orthopedic surgeons and pathologists is mandatory to verify these diagnoses.

  6. Marble Bone Disease: A Rare Bone Disorder

    PubMed Central

    Harinathbabu, Maheswari; Thillaigovindan, Ranjani; Prabhu, Geetha

    2015-01-01

    Osteopetrosis, or marble bone disease, is a rare skeletal disorder due to a defective function of the osteoclasts. This defect renders bones more susceptible to osteomyelitis due to decreased vascularity. This disorder is inherited as autosomal dominant and autosomal recessive. Healthcare professionals should urge these patients to maintain their oral health as well as general health, as this condition makes these patients more susceptible to frequent infections and fractures. This case report emphasizes the signs and symptoms of marble bone disease and presents clinical and radiographic findings.  PMID:26594603

  7. Genetics Home Reference: Paget disease of bone

    MedlinePlus

    ... Conditions Paget disease of bone Paget disease of bone Enable Javascript to view the expand/collapse boxes. ... Open All Close All Description Paget disease of bone is a disorder that causes bones to grow ...

  8. Diagnosis of metabolic bone disease

    SciTech Connect

    Grech, P.; Martin, T.J.; Barrington, N.A.; Ell, P.J.

    1986-01-01

    This book presents a reference on the radiologic evaluation, features, and differential diagnosis of metabolic diseases involving the whole skeleton, calcium deficiencies resulting from pharmacologic agents, and bone changes related to endocrine disturbances. It also stresses how radiology, nuclear medicine, and biochemistry - either alone or in concert - contribute to clinical diagnosis. It covers renal bone disease, Paget's disease, hyperphosphatasia, extraskeletal mineralization, metabolic bone disorders related to malnutrition, tumors, plus radionuclide studies including materials and methods.

  9. Theoretical effects of fully ductile versus fully brittle behaviors of bone tissue on the strength of the human proximal femur and vertebral body.

    PubMed

    Nawathe, Shashank; Yang, Haisheng; Fields, Aaron J; Bouxsein, Mary L; Keaveny, Tony M

    2015-05-01

    The influence of the ductility of bone tissue on whole-bone strength represents a fundamental issue of multi-scale biomechanics. To gain insight, we performed a computational study of 16 human proximal femurs and 12 T9 vertebral bodies, comparing the whole-bone strength for the two hypothetical bounding cases of fully brittle versus fully ductile tissue-level failure behaviors, all other factors, including tissue-level elastic modulus and yield stress, held fixed. For each bone, a finite element model was generated (60-82 μm element size; up to 120 million elements) and was virtually loaded in habitual (stance for femur, compression for vertebra) and non-habitual (sideways fall, only for femur) loading modes. Using a geometrically and materially non-linear model, the tissue was assumed to be either fully brittle or fully ductile. We found that, under habitual loading, changing the tissue behavior from fully ductile to fully brittle reduced whole-bone strength by 38.3±2.4% (mean±SD) and 39.4±1.9% for the femur and vertebra, respectively (p=0.39 for site difference). These reductions were remarkably uniform across bones, but (for the femur) were greater for non-habitual (57.1±4.7%) than habitual loading (p<0.001). At overall structural failure, there was 5-10-fold less failed tissue for the fully brittle than fully ductile cases. These theoretical results suggest that the whole-bone strength of the proximal femur and vertebra can vary substantially between fully brittle and fully ductile tissue-level behaviors, an effect that is relatively insensitive to bone morphology but greater for non-habitual loading.

  10. Polarization in Raman spectroscopy helps explain bone brittleness in genetic mouse models

    NASA Astrophysics Data System (ADS)

    Makowski, Alexander J.; Pence, Isaac J.; Uppuganti, Sasidhar; Zein-Sabatto, Ahbid; Huszagh, Meredith C.; Mahadevan-Jansen, Anita; Nyman, Jeffry S.

    2014-11-01

    Raman spectroscopy (RS) has been extensively used to characterize bone composition. However, the link between bone biomechanics and RS measures is not well established. Here, we leveraged the sensitivity of RS polarization to organization, thereby assessing whether RS can explain differences in bone toughness in genetic mouse models for which traditional RS peak ratios are not informative. In the selected mutant mice-activating transcription factor 4 (ATF4) or matrix metalloproteinase 9 (MMP9) knock-outs-toughness is reduced but differences in bone strength do not exist between knock-out and corresponding wild-type controls. To incorporate differences in the RS of bone occurring at peak shoulders, a multivariate approach was used. Full spectrum principal components analysis of two paired, orthogonal bone orientations (relative to laser polarization) improved genotype classification and correlation to bone toughness when compared to traditional peak ratios. When applied to femurs from wild-type mice at 8 and 20 weeks of age, the principal components of orthogonal bone orientations improved age classification but not the explanation of the maturation-related increase in strength. Overall, increasing polarization information by collecting spectra from two bone orientations improves the ability of multivariate RS to explain variance in bone toughness, likely due to polarization sensitivity to organizational changes in both mineral and collagen.

  11. Calcium and bone disease

    PubMed Central

    Blair, Harry C.; Robinson, Lisa J.; Huang, Christopher L.-H.; Sun, Li; Friedman, Peter A.; Schlesinger, Paul H.; Zaidi, Mone

    2013-01-01

    Calcium transport and calcium signaling are of basic importance in bone cells. Bone is the major store of calcium and a key regulatory organ for calcium homeostasis. Bone, in major part, responds to calcium-dependent signals from the parathyroids and via vitamin D metabolites, although bone retains direct response to extracellular calcium if parathyroid regulation is lost. Improved understanding of calcium transporters and calcium-regulated cellular processes has resulted from analysis of genetic defects, including several defects with low or high bone mass. Osteoblasts deposit calcium by mechanisms including phosphate and calcium transport with alkalinization to absorb acid created by mineral deposition; cartilage calcium mineralization occurs by passive diffusion and phosphate production. Calcium mobilization by osteoclasts is mediated by acid secretion. Both bone forming and bone resorbing cells use calcium signals as regulators of differentiation and activity. This has been studied in more detail in osteoclasts, where both osteoclast differentiation and motility are regulated by calcium. PMID:21674636

  12. Oral Health and Bone Disease

    MedlinePlus

    ... and ill-fitting or loose dentures. Effects of Osteoporosis Treatments on Oral Health It is not known ... Resources For more information on osteoporosis, visit: NIH Osteoporosis and Related Bone Diseases ~ National Resource Center Website: ...

  13. Bone disease and HIV infection.

    PubMed

    Amorosa, Valerianna; Tebas, Pablo

    2006-01-01

    The high prevalence of bone demineralization among human immunodeficiency virus (HIV)-infected patients in the current therapeutic era has been described in multiple studies, sounding the alarm that we may expect an epidemic of fragility fractures in the future. However, despite noting high overall prevalences of osteopenia and osteoporosis, recent longitudinal studies that we review here have generally not observed accelerated bone loss during antiretroviral therapy beyond the initial period after treatment initiation. We discuss the continued progress toward understanding the mechanisms of HIV-associated bone loss, particularly the effects of HIV infection, antiretroviral therapy, and host immune factors on bone turnover. We summarize results of clinical trials published in the past year that studied the safety and efficacy of treatment of bone loss in HIV-infected patients and provide provisional opinions about who should be considered for bone disease screening and treatment.

  14. [Metabolic bone and joint diseases].

    PubMed

    Endo, Itsuro

    2014-10-01

    Metabolic bone and joint diseases in adults include osteomalacia, rheumatoid arthritis, gouty arthritis. Recently, the newest molecular biology procedures and the clinical observation studies can produce good results for understanding of these diseases. From this perspective, the author introduced updated information of the pathophysiology, the latest diagnostic criteria and the therapy of these diseases.

  15. Hyponatremia and bone disease.

    PubMed

    Negri, Armando Luis; Ayus, Juan Carlos

    2016-09-24

    Hip fractures represent a serious health risk in the elderly, causing substantial morbidity and mortality. There is now a considerable volume of literature suggesting that chronic hyponatremia increases the adjusted odds ratio (OR) for both falls and fractures in the elderly. Hyponatremia appears to contribute to falls and fractures by two mechanisms. First, it produces mild cognitive impairment, resulting in unsteady gait and falls; this is probably due to the loss of glutamate (a neurotransmitter involved in gait function) as an osmolyte during brain adaptation to chronic hyponatremia. Second, hyponatremia directly contributes to osteoporosis and increased bone fragility by inducing increased bone resorption to mobilize sodium stores in bone. Low extracellular sodium directly stimulates osteoclastogenesis and bone resorptive activity through decreased cellular uptake of ascorbic acid and the induction of oxidative stress; these effects occur in a sodium level-dependent manner. Hyponatremic patients have elevated circulating arginine-vasopressin (AVP) levels, and AVP acting on two receptors expressed in osteoblasts and osteoclasts, Avpr1α and Avpr2, can increase bone resorption and decrease osteoblastogenesis. Should we be screening for low serum sodium in patients with osteoporosis or assessing bone mineral density (BMD) in patients with hyponatremia? The answers to these questions have not been established. Definitive answers will require randomized controlled studies that allocate elderly individuals with mild hyponatremia to receive either active treatment or no treatment for hyponatremia, to determine whether correction of hyponatremia prevents gait disturbances and changes in BMD, thereby reducing the risk of fractures. Until such studies are conducted, physicians caring for elderly patients must be aware of the association between hyponatremia and bone disorders. As serum sodium is a readily available, simple, and affordable biochemical measurement

  16. Bone Disease in Multiple Myeloma.

    PubMed

    Eda, Homare; Santo, Loredana; David Roodman, G; Raje, Noopur

    2016-01-01

    Bone involvement represented by osteolytic bone disease (OBD) or osteopenia is one of the pathognomonic and defining characteristics of multiple myeloma (MM). Nearly 90 % of patients with MM develop osteolytic bone lesions, frequently complicated by skeletal-related events (SRE) such as severe bone pain, pathological fractures, vertebral collapse, hypercalcemia, and spinal cord compression. All of these not only result in a negative impact on quality of life but also adversely impact overall survival. OBD is a consequence of increased osteoclast (OC) activation along with osteoblast (OB) inhibition, resulting in altered bone remodeling. OC number and activity are increased in MM via cytokine deregulation within the bone marrow (BM) milieu, whereas negative regulators of OB differentiation suppress bone formation. Inhibition of osteolysis and stimulation of OB differentiation leads to reduced tumor growth in vivo. Therefore, novel agents targeting OBD are promising therapeutic strategies not only for the treatment of MM OBD but also for the treatment of MM. Several novel agents in addition to bisphosphonates are currently under investigation for their positive effect on bone remodeling via OC inhibition or OB stimulation. Future studies will look to combine or sequence all of these agents with the goal of not only alleviating morbidity from MM OBD but also capitalizing on the resultant antitumor activity.

  17. What Is Paget's Disease of Bone?

    MedlinePlus

    ... About Paget’s Disease and Other Related Conditions: NIH Osteoporosis and Related Bone Diseases ~ National Resource Center 2 ... org) in the preparation of this publication. NIH Osteoporosis and Related Bone Diseases ~ National Resource Center 2 ...

  18. FGF23 associated bone diseases.

    PubMed

    Liao, Eryuan

    2013-03-01

    Recently, fibroblast growth factor 23 (FGF23) has sparked widespread interest because of its potential role in regulating phosphate and vitamin D metabolism. In this review, we summarized the FGF superfamily, the mechanism of FGF23 on phosphate and vitamin D metabolism, and the FGF23 related bone disease.

  19. Denosumab for bone diseases: translating bone biology into targeted therapy.

    PubMed

    Tsourdi, Elena; Rachner, Tilman D; Rauner, Martina; Hamann, Christine; Hofbauer, Lorenz C

    2011-12-01

    Signalling of receptor activator of nuclear factor-κB (RANK) ligand (RANKL) through RANK is a critical pathway to regulate the differentiation and activity of osteoclasts and, hence, a master regulator of bone resorption. Increased RANKL activity has been demonstrated in diseases characterised by excessive bone loss such as osteoporosis, rheumatoid arthritis and osteolytic bone metastases. The development and approval of denosumab, a fully MAB against RANKL, has heralded a new era in the treatment of bone diseases by providing a potent, targeted and reversible inhibitor of bone resorption. This article summarises the molecular and cellular biology of the RANKL/RANK system and critically reviews preclinical and clinical studies that have established denosumab as a promising novel therapy for metabolic and malignant bone diseases. We will discuss the potential indications for denosumab along with a critical review of safety and analyse its potential within the concert of established therapies.

  20. Pain and Paget's Disease of Bone

    MedlinePlus

    ... Home Paget’s Disease of Bone Paget’s Disease Management Pain and Paget’s Disease of Bone Publication available in: ... focus(); */ } //--> Print-Friendly Page May 2015 Types of Pain Paget’s disease can cause several different kinds of ...

  1. [Cytokines in bone diseases. Wnt signal and excessive bone formation].

    PubMed

    Hosoi, Takayuki

    2010-10-01

    Wnt signal has been known to play various roles in many organ from the beginning of embryogensis. Its role in bone metabolism has also been investigated and established. Lipoprotein receptor-related protein 5 (LRP5) is one of the important molecules in wnt signal pathway whose point mutations are related to both bone loss and excessive bone formation. Wnt signal is involved in the action of sclerostin which was found as a gene for osteosclerosis, one of the diseases of excessive bone formation. Wnt signal is keeping the position as an important research target for normal and pathological bone formation.

  2. Photodynamic therapy of diseased bone

    NASA Astrophysics Data System (ADS)

    Bisland, Stuart K.; Yee, Albert; Siewerdsen, Jeffery; Wilson, Brian C.; Burch, Shane

    2005-08-01

    Objective: Photodynamic therapy (PDT) defines the oxygen-dependent reaction that occurs upon light-mediated activation of a photosensitizing compound, culminating in the generation of cytotoxic, reactive oxygen species, predominantly, singlet oxygen. We are investigating PDT treatment of diseased bone. Methods: Using a rat model of human breast cancer (MT-1)-derived bone metastasis we confirmed the efficacy of benzoporphyrin-derivative monoacid (BPD-MA)-PDT for treating metastatic lesions within vertebrae or long bones. Results: Light administration (150 J) 15 mins after BPDMA (2.5 mg/Kg, i.v.) into the lumbar (L3) vertebra of rats resulted in complete ablation of the tumour and surrounding bone marrow 48 hrs post-PDT without paralysis. Porcine vertebrae provided a model comparable to that of human for light propagation (at 150 J/cm) and PDT response (BPD-MA; 6 mg/m2, i.v.) in non-tumour vertebrae. Precise fibre placement was afforded by 3-D cone beam computed tomography. Average penetration depth of light was 0.16 +/- 0.04 cm, however, the necrotic/non-necrotic interface extended 0.6 cm out from the treatment fiber with an average incident fluence rate of 4.3 mW/cm2. Non-necrotic tissue damage was evident 2 cm out from the treatment fiber. Current studies involving BPD-MA-PDT treatment of primary osteosarcomas in the forelimbs of dogs are very promising. Magnetic resonance imaging 24 hr post treatment reveal well circumscribed margins of treatment that encompass the entire 3-4 cm lesion. Finally, we are also interested in using 5-aminolevulinic acid (ALA) mediated PDT to treat osteomyelitis. Response to therapy was monitored as changes in bioluminescence signal of staphylococcus aureus (SA)-derived biofilms grown onto 0.5 cm lengths of wire and subjected to ALA-PDT either in vitro or in vivo upon implant into the intramedullary space of rat tibia. Transcutaneous delivery of PDT (75 J/cm2) effectively eradicated SAbiofilms within bone. Conclusions: Results support

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

    PubMed

    Ito, Akemi; Yajima, Aiji

    2011-09-01

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

  4. MiRNAs in bone diseases.

    PubMed

    Moore, Benjamin T; Xiao, Peng

    2013-01-01

    MicroRNAs (miRNAs), which mainly inhibit protein expression by targeting the 3'UTR (untranslated region) of mRNAs, are known to play various roles in the pathogenesis of many different types of diseases. Specifically, in bone diseases, recent emphasis has been placed on the involvement of miRNAs in the differentiation and proliferation of bone and cartilage cells, particularly with regards to how these mechanisms contribute to bone homeostasis. In this review, we summarize miRNAs that are important in the differentiation and proliferation of bone cells, and specific miRNAs associated with bone diseases, such as osteoporosis, osteoarthritis and rheumatoid arthritis. This review also provides the perspective that miRNA studies will identify not only new mechanisms in basic bone research, but also potential novel diagnostic biomarkers and drug targets for bone diseases.

  5. Mesenchymal stem cells for bone repair and metabolic bone diseases.

    PubMed

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

    2009-10-01

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

  6. Mesenchymal Stem Cells for Bone Repair and Metabolic Bone Diseases

    PubMed Central

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

    2009-01-01

    Human mesenchymal stem cells offer a potential alternative to embryonic stem cells in clinical applications. The ability of these cells to self-renew and differentiate into multiple tissues, including bone, cartilage, fat, and other tissues of mesenchymal origin, makes them an attractive candidate for clinical applications. Patients who experience fracture nonunion and metabolic bone diseases, such as osteogenesis imperfecta and hypophosphatasia, have benefited from human mesenchymal stem cell therapy. Because of their ability to modulate immune responses, allogeneic transplant of these cells may be feasible without a substantial risk of immune rejection. The field of regenerative medicine is still facing considerable challenges; however, with the progress achieved thus far, the promise of stem cell therapy as a viable option for fracture nonunion and metabolic bone diseases is closer to reality. In this review, we update the biology and clinical applicability of human mesenchymal stem cells for bone repair and metabolic bone diseases. PMID:19797778

  7. [Hearing and balance in metabolic bone diseases].

    PubMed

    Zatoński, Tomasz; Temporale, Hanna; Krecicki, Tomasz

    2012-03-01

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

  8. Role of RANKL in bone diseases.

    PubMed

    Anandarajah, Allen P

    2009-03-01

    Bone remodeling is a tightly regulated process of osteoclast-mediated bone resorption, balanced by osteoblast-mediated bone formation. Disruption of this balance can lead to increased bone turnover, resulting in excessive bone loss or extra bone formation and consequent skeletal disease. The receptor activator of nuclear factor kappaB ligand (RANKL) (along with its receptor), the receptor activator of nuclear factor kappaB and its natural decoy receptor, osteoprotegerin, are the final effector proteins of osteoclastic bone resorption. Here, I provide an overview of recent studies that highlight the key role of RANKL in the pathophysiology of several bone diseases and discuss the novel therapeutic approaches afforded by the modulation of RANKL.

  9. Roles of leptin in bone metabolism and bone diseases.

    PubMed

    Chen, Xu Xu; Yang, Tianfu

    2015-09-01

    Adipose tissue has been more accepted as an active contributor to whole body homeostasis, rather than just a fat depot, since leptin, a 16 kDa protein, was discovered as the product of the obese gene in 1994. With more and more studies conducted on this hormone, it has been shown that there is a close relationship between adipose tissue and bone, which have important effects on each other. Bone is the source of many hormones, such as osteocalcin, that can affect energy metabolism and then the anabolism or catabolism of fat tissue. In contrast, the adipose tissue synthesizes and releases a series of adipokines, which are involved in bone metabolism through direct or indirect effects on bone formation and resorption. Interestingly, leptin, one of the most important cytokines derived from fat tissue, seems to account for the largest part of effects on bone, through direct or indirect involvement in bone remodeling and by playing a significant role in many bone diseases, such as osteoporosis, osteoarthritis, rheumatic arthritis, bone tumors and even fractures. In this review, we will discuss the progress in leptin research, particularly focusing on the roles of leptin in bone diseases.

  10. Black bone disease in a healing fracture.

    PubMed

    Thiam, Desmond; Teo, Tse Yean; Malhotra, Rishi; Tan, Kong Bing; Chee, Yu Han

    2016-01-28

    Black bone disease refers to the hyperpigmentation of bone secondary to prolonged usage of minocycline. We present a report of a 34-year-old man who underwent femoral shaft fracture fixation complicated by deep infection requiring debridement. The implants were removed 10 months later after long-term treatment with minocycline and fracture union. A refracture of the femoral shaft occurred 2 days after implant removal and repeat fixation was required. Intraoperatively, abundant heavily pigmented and dark brown bone callus was noted over the old fracture site. There was no evidence of other bony pathology and the appearance was consistent with minocycline-associated pigmentation. As far as we are aware, this is the first case of black bone disease affecting callus within the interval period of bone healing. We also discuss the relevant literature on black bone disease to bring light on this rare entity that is an unwelcomed surprise to operating orthopaedic surgeons.

  11. [Serum sclerostin levels and metabolic bone diseases].

    PubMed

    Yamauchi, Mika; Sugimoto, Toshitsugu

    2013-06-01

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

  12. [Clinical condition and therapy of bone diseases].

    PubMed

    Miura, Kohji; Oznono, Keiichi

    2013-12-01

    Skeletal dysplasia is the term which represents disorders including growth and differentiation of bone, cartilage and ligament. A lot of diseases are included, and new disorders have been added. However, the therapy of most bone diseases is less well-established. Achondroplasia, hypochondroplasia, and osteogenesis imperfecta are most frequent bone diseases. There is no curative treatment for these diseases, however, supportive therapies are available ; for example, growth-hormone therapy for achondroplasia and hypochondroplasia, and bisphosphonate therapy for osteogenesis imperfecta. In addition, enzyme replacement therapy for hypophosphatasia is now on clinical trial.

  13. Increasing duration of type 1 diabetes perturbs the strength-structure relationship and increases brittleness of bone.

    PubMed

    Nyman, Jeffry S; Even, Jesse L; Jo, Chan-Hee; Herbert, Erik G; Murry, Matthew R; Cockrell, Gael E; Wahl, Elizabeth C; Bunn, R Clay; Lumpkin, Charles K; Fowlkes, John L; Thrailkill, Kathryn M

    2011-04-01

    Type 1 diabetes (T1DM) increases the likelihood of a fracture. Despite serious complications in the healing of fractures among those with diabetes, the underlying causes are not delineated for the effect of diabetes on the fracture resistance of bone. Therefore, in a mouse model of T1DM, we have investigated the possibility that a prolonged state of diabetes perturbs the relationship between bone strength and structure (i.e., affects tissue properties). At 10, 15, and 18 weeks following injection of streptozotocin to induce diabetes, diabetic male mice and age-matched controls were examined for measures of skeletal integrity. We assessed 1) the moment of inertia (I(MIN)) of the cortical bone within diaphysis, trabecular bone architecture of the metaphysis, and mineralization density of the tissue (TMD) for each compartment of the femur by micro-computed tomography and 2) biomechanical properties by three-point bending test (femur) and nanoindentation (tibia). In the metaphysis, a significant decrease in trabecular bone volume fraction and trabecular TMD was apparent after 10 weeks of diabetes. For cortical bone, type 1 diabetes was associated with decreased cortical TMD, I(MIN), rigidity, and peak moment as well as a lack of normal age-related increases in the biomechanical properties. However, there were only modest differences in material properties between diabetic and normal mice at both whole bone and tissue-levels. As the duration of diabetes increased, bone toughness decreased relative to control. If the sole effect of diabetes on bone strength was due to a reduction in bone size, then I(MIN) would be the only significant variable explaining the variance in the maximum moment. However, general linear modeling found that the relationship between peak moment and I(MIN) depended on whether the bone was from a diabetic mouse and the duration of diabetes. Thus, these findings suggest that the elevated fracture risk among diabetics is impacted by complex changes

  14. Bone Disease and Idiopathic Hypercalciuria

    PubMed Central

    Zerwekh, Joseph E.

    2008-01-01

    Observational and epidemiological studies alike have demonstrated that idiopathic hypercalciuric (IH) stone-forming patients typically demonstrate bone mineral density scores significantly less than those observed for age- and gender-matched normal subjects or those for non-hypercalciuric stone-forming patients. Most of these studies have relied on changes in bone mineral density (BMD) and have not explored the mechanism(s) involved. There have been a small number of studies that have relied on dynamic bone histomorphometry to ascertain the nature of the bone defect in IH patients. When performed, these studies have clearly demonstrated increased bone resorption and high bone turnover in patients with fasting hypercalciuria while suppressed bone formation indices are the most consistent finding in patients with the absorptive variant of IH. The causes of this apparent difference in bone remodeling between the two variants of IH is still uncertain. Available evidence suggests that potential mechanisms may be dependent in large part to genetic, metabolic, and nutritional causes of hypercalciuria and bone loss in patients with IH. PMID:18359394

  15. [Is bone biopsy necessary for the diagnosis of metabolic bone diseases? Non- invasive assessment of bone turn over markers could define the cause of metabolic bone diseases].

    PubMed

    Suzuki, Atsushi

    2011-09-01

    Recent advances of the measurement of bone turn over markers contribute to non-invasive assessment of bone-metabolic disorders. We can detect the cause of the metabolic disorders with bone turn over markers and hormonal profiles more easily than before. Today, we can diagnose and treat metabolic bone diseases without invasive procedure such as bone biopsy.

  16. Myeloma and bone disease: "the dangerous tango".

    PubMed

    Epstein, Joshua; Walker, Ronald

    2006-04-01

    Osteolytic bone disease is the most debilitating manifestation of myeloma. However, myeloma-induced effects on the bone-active cells in the bone marrow are more than just a manifestation of disease--the myeloma derives essential support from the changed balance between bone-forming and -resorbing cells. This observation has lead to the notion that effective control of myeloma bone disease by reducing osteoclast activity and restoring osteoblast activity will contribute to long-term control of myeloma progression. Unlike osteolysis associated with other tumors that metastasize to bone, myeloma-associated lytic lesions are unique in that they do not repair even after many years in complete remission, reflecting a total loss of osteoblastic activity in areas of myeloma foci, apparently induced by the myeloma. Advances in imaging technology including positron emission tomography-computed tomography scanning allows accurate detection of lytic lesions and the monitoring of treatment effects. Effective antimyeloma therapy combined with anti-osteoclast drugs can halt the progression of osteolysis; in severe cases with vertebral compression fractures, effective physical support in the form of vertebroplasty or kyphoplasty is required for control of function, pain, and stature. Fractures of the long bones are usually treated by intramedullary rod placement. New approaches to enhance osteoblast activity while controlling osteoclast activity currently under investigation may prove effective in controlling lytic bone disease and myeloma progression.

  17. Bone Diseases - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Bone Diseases URL of this page: https://medlineplus.gov/languages/bonediseases.html Other topics A-Z A B ...

  18. Crosslink in bone collagen in Paget's disease.

    PubMed Central

    Misra, D P

    1975-01-01

    The crosslink in bone collagen was analysed in specimens of bone obtained at necropsy from cases of Paget's disease and compared with normal bone collagen of the same age. The specimens were stored at -20 degrees C before analysis. The predominant crosslink in a normal bone collagen was hydroxylysinohydroxynorleucine (di OH-LNL) (F1), which was designated syndesine in the past; another fraction, hydroxylysinorleucine (HLNL) (F2), musch less prominent than di OH-LNL, was also noted in a normal bone collagen. Both fractions were reduced in bone tissue of advancing age. The peak corresponding to HLNL was considerably increased in Paget's disease. This abnormality was constantly seen in specimens of bone from cases of Paget's disease, but the significance of the finging could not be assessed from the present investigation. Calcitonin has been shown to produce complete remission in Paget's disease and the crosslink pattern was found to be normal in specimens examined froma calcitonin-treated patient. This shows that calcitonin has some effect on the metabolism of collagen and a normal crosslink in such a situation lends support to this idea. PMID:1127123

  19. Periodontal disease in Paget’s disease of bone

    PubMed Central

    Nuti, Niccolò; Ferrari, Marco

    2015-01-01

    Summary A 59-year-old man suffering from Paget’s disease of bone and periodontal disease was examined in anticipation of bisphosphonate treatment. The previous therapy with clodronate resulted ineffective and markers of bone turnover were markedly elevated. Periodontal disease was correctly approached and treated with an excellent outcome. 5 mg zoledronate iv infusion induced a remarkable reduction of bone markers which persisted on time within the normal range. After zoledronate treatment no signs of osteonecrosis of the jaw (ONJ) were observed. A correct management of periodontal disease is mandatory in pagetic patients on bisphosphonate treatment. PMID:26604949

  20. Recent developments in metabolic bone diseases: a gnathic perspective.

    PubMed

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

    2014-12-01

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

  1. Bone disease in pediatric rheumatologic disorders.

    PubMed

    Burnham, Jon M; Leonard, Mary B

    2004-02-01

    Children with rheumatic disorders have multiple risk factors for impaired bone health, including delayed growth and development, malnutrition, decreased weight-bearing activity, inflammation, and glucocorticoid therapy. The impact of rheumatic disease during childhood may be immediate, resulting in fragility fractures, or delayed, because of suboptimal peak bone mass accrual. Recent years have seen increased interest in the effects of pediatric rheumatic disorders on bone mineralization, such as juvenile rheumatoid arthritis, systemic lupus erythematosus, and juvenile dermatomyositis. This review outlines the expected gains in bone size and mass during childhood and adolescence, and summarizes the advantages and disadvantages of available technologies for the assessment of skeletal growth and fragility in children. The varied threats to bone health in pediatric rheumatic disorders are reviewed, with emphasis on recent insights into the molecular mechanisms of inflammation-induced bone resorption. The literature assessing bone deficits and risk factors for impaired bone health in pediatric rheumatic disorders is reviewed, with consideration of the strengths and limitations of prior studies. Finally, future research directions are proposed.

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

    MedlinePlus

    ... For more information about Paget’s disease , contact: NIH Osteoporosis and Related Bone Diseases ~ National Resource Center Website: ... drug products. NIH Pub. No. 15-7919 NIH Osteoporosis and Related Bone Diseases ~ National Resource Center 2 ...

  3. Paget's Disease of Bone: Approach to Its Historical Origins.

    PubMed

    Menéndez-Bueyes, Luis R; Soler Fernández, María Del Carmen

    Paget's disease of bone is the second most common bone disease after osteoporosis. It is characterized by focal regions of highly exaggerated bone remodeling, with abnormalities in all phases of the remodeling process. This study aims to investigate the hypothesis of a possible British origin of Paget's disease of bone by studying the worldwide geographic distribution of cases identified in ancient skeletons excavated from archaeological sites. The methodology consists in reviewing cases of Paget's disease of bone described in the literature.

  4. Nanotechnology controlled drug delivery for treating bone diseases.

    PubMed

    Yang, Lei; Webster, Thomas J

    2009-08-01

    Rapid developments at the intersection of nanotechnology and controlled drug delivery have triggered exceptional growth in treating various bone diseases. As a result, over the past decade, nanotechnology has contributed tremendously to controlling drug delivery for treating various bone diseases, and in many cases, has led to increased bone regeneration. In this review paper, the recent experimental progress towards using nanotechnology to treat bone-specific diseases is reviewed. Novel applications of different types of nanomaterials (from nanoparticles to 3D nanostructured scaffolds) for treating bone diseases are summarized. In addition, fundamental principles for utilizing nanomaterials to create better drug delivery systems, especially for treating bone diseases and regenerating bone, are emphasized.

  5. Cat-scratch disease and bone scintigraphy.

    PubMed

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

    2012-08-01

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

  6. 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.

  7. Paget's disease of bone (osteitis deformans).

    PubMed

    Ankrom, M A; Shapiro, J R

    1998-08-01

    Paget's disease of bone is important in geriatric populations because it is the second most common bone disorder after osteoporosis. In older people, it may be responsible for chronic back pain and joint pain, skeletal deformities, hearing loss, and cranial nerve compression. Paget's disease can reduce both function and mobility in the older people. In addition to newer tests for assessing the activity of Paget's disease, effective therapy is available in the form of salmon calcitonin for nasal administration and new third generation bisphosphonates. Frequently, treatment can reverse the course of the disease. For these reasons, it is feasible for the physician to adopt an aggressive approach to diagnosis and treatment. The objective should be to relieve pain, improve mobility, and forestall debilitating complications. This review will focus on the manifestations and clinical management of Paget's disease. Two cases are presented that illustrate common management problems in older patients.

  8. [Cytokines in bone diseases. Anti-cytokine therapies for bone and joint diseases].

    PubMed

    Tanaka, Yoshiya

    2010-10-01

    The efficacy of biologics targeting inflammatory cytokines such as TNF and IL-6 for bone and joint diseases has been emerging. Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic synovitis and bone damage. By the use of TNF-inhibitors, clinical remission, structural remission and functional remission have become possible during the treatment of RA. Especially, the progress of joint and bone destruction is completely suppressed by TNF-inhibitors in the vast majority of RA patients. On the other hand, anti-RANKL antibody inhibits joint destruction as well as systemic osteoporosis, though no effects on synovitis of RA. Thus, differential efficacy of different therapies in bone destruction and osteoporosis would warrant further study to clarify the mechanisms of bone and joints diseases.

  9. [Syringomyelia and associated bone and joint diseases].

    PubMed

    Alnot, J-Y; Rossarie, R; Welby, F

    2007-05-01

    Syringomyelia can occur in patients presenting bone and joint diseases of various origins. When joint destruction of the shoulder or elbow produces little pain, a neurological cause might be involved. In this case, the disease history can be of utmost importance because an initial diagnosis of rheumatoid polyarthritis, polyosteoarthritis, or destructive joint disease can be misleading before the syringomyelic origin of the bone and joint disease becomes patent. We report two cases illustrating this association and the diagnostic pitfalls which can delay recognition of the syringomyelia. Better awareness of the prevalence of this condition should be helpful in establishing the diagnosis and in selecting patients who can benefit from neurosurgical treatment. The two cases presented here suggest that syringomyelia could be underdiagnosed in certain patients with an initially atypical presentation. A review of the current knowledge of syringomyelia suggests that arthroplasty is generally not advisable for destroyed dislocated syringomyelic joints.

  10. Nuclear Receptors in Bone Physiology and Diseases

    PubMed Central

    Youn, Min-Young; Inoue, Kazuki; Takada, Ichiro; Kouzmenko, Alexander; Kato, Shigeaki

    2013-01-01

    During the last decade, our view on the skeleton as a mere solid physical support structure has been transformed, as bone emerged as a dynamic, constantly remodeling tissue with systemic regulatory functions including those of an endocrine organ. Reflecting this remarkable functional complexity, distinct classes of humoral and intracellular regulatory factors have been shown to control vital processes in the bone. Among these regulators, nuclear receptors (NRs) play fundamental roles in bone development, growth, and maintenance. NRs are DNA-binding transcription factors that act as intracellular transducers of the respective ligand signaling pathways through modulation of expression of specific sets of cognate target genes. Aberrant NR signaling caused by receptor or ligand deficiency may profoundly affect bone health and compromise skeletal functions. Ligand dependency of NR action underlies a major strategy of therapeutic intervention to correct aberrant NR signaling, and significant efforts have been made to design novel synthetic NR ligands with enhanced beneficial properties and reduced potential negative side effects. As an example, estrogen deficiency causes bone loss and leads to development of osteoporosis, the most prevalent skeletal disorder in postmenopausal women. Since administration of natural estrogens for the treatment of osteoporosis often associates with undesirable side effects, several synthetic estrogen receptor ligands have been developed with higher therapeutic efficacy and specificity. This review presents current progress in our understanding of the roles of various nuclear receptor-mediated signaling pathways in bone physiology and disease, and in development of advanced NR ligands for treatment of common skeletal disorders. PMID:23589826

  11. Diabetes mellitus related bone metabolism and periodontal disease

    PubMed Central

    Wu, Ying-Ying; Xiao, E; Graves, Dana T

    2015-01-01

    Diabetes mellitus and periodontal disease are chronic diseases affecting a large number of populations worldwide. Changed bone metabolism is one of the important long-term complications associated with diabetes mellitus. Alveolar bone loss is one of the main outcomes of periodontitis, and diabetes is among the primary risk factors for periodontal disease. In this review, we summarise the adverse effects of diabetes on the periodontium in periodontitis subjects, focusing on alveolar bone loss. Bone remodelling begins with osteoclasts resorbing bone, followed by new bone formation by osteoblasts in the resorption lacunae. Therefore, we discuss the potential mechanism of diabetes-enhanced bone loss in relation to osteoblasts and osteoclasts. PMID:25857702

  12. Diabetes mellitus related bone metabolism and periodontal disease.

    PubMed

    Wu, Ying-Ying; Xiao, E; Graves, Dana T

    2015-06-26

    Diabetes mellitus and periodontal disease are chronic diseases affecting a large number of populations worldwide. Changed bone metabolism is one of the important long-term complications associated with diabetes mellitus. Alveolar bone loss is one of the main outcomes of periodontitis, and diabetes is among the primary risk factors for periodontal disease. In this review, we summarise the adverse effects of diabetes on the periodontium in periodontitis subjects, focusing on alveolar bone loss. Bone remodelling begins with osteoclasts resorbing bone, followed by new bone formation by osteoblasts in the resorption lacunae. Therefore, we discuss the potential mechanism of diabetes-enhanced bone loss in relation to osteoblasts and osteoclasts.

  13. An Insight in to Paget's Disease of Bone

    PubMed Central

    Sabharwal, Robin; Gupta, Shivangi; Sepolia, Shipra; Panigrahi, Rajat; Mohanty, Saumyakanta; Subudhi, Santosh Kumar; Kumar, Manish

    2014-01-01

    Paget's disease of bone (PDB) is a common disorder which may affect one or many bones. Although many patients are asymptomatic, a variety of symptoms and complications may occur. PDB is a focal disorder of bone turnover characterized by excessive bone resorption coupled with bone formation. PDB begins with a period of increased osteoclastic activity and bone resorption, followed by increased osteoblast production of woven bone that is poorly mineralized. In the final phase of the disease process, dense cortical and trabecular bone deposition predominates, but the bone is sclerotic and poorly organized and lacks the structural integrity and strength of normal bone. This article briefly reviews the etiopathogenesis, clinical radiographic and histological features of Paget's disease. PMID:24665195

  14. Fracture, aging and disease in bone

    SciTech Connect

    Ager, J.W.; Balooch, G.; Ritchie, R.O.

    2006-02-01

    fracture resistance, whereas regulating the level of the cytokine TGF-beta can offer significant improvements in the stiffness, strength and toughness of bone, and as such may be considered as a therapeutic target to treat increased bone fragility induced by aging, drugs, and disease.

  15. GORHAM-STOUT SYNDROME: PHANTOM BONE DISEASE

    PubMed Central

    El-Kouba, Gabriel; de Araújo Santos, Romilton; Pilluski, Paulo César; Severo, Antonio; Lech, Osvandré

    2015-01-01

    Gorham-Stout syndrome is a disease that presents idiopathic osteolysis of a bone or closely contiguous area. The etiology is unknown. It is a rare condition that is difficult to diagnose, and its treatment is controversial. It affects individuals irrespective of age or sex. In this study, we conducted a bibliographic review of the disease, specifically focusing on the differential diagnosis, and we demonstrated the follow-up on a patient with this syndrome from the time of its diagnosis, through treatment, to its current state of evolution. PMID:27026974

  16. MicroRNAs in bone diseases.

    PubMed

    Gennari, L; Bianciardi, S; Merlotti, D

    2017-04-01

    MicroRNAs are small, noncoding single-stranded RNAs that have emerged as important posttranscriptional regulators of gene expression, with an essential role in vertebrate development and different biological processes. This review highlights the recent advances in the function of miRNAs and their roles in bone remodeling and bone diseases. MicroRNAs (miRNAs) are a class of small (∼22 nt), noncoding single-stranded RNAs that have emerged as important posttranscriptional regulators of gene expression. They are essential for vertebrate development and play critical roles in different biological processes related to cell differentiation, activity, metabolism, and apoptosis. A rising number of experimental reports now indicate that miRNAs contribute to every step of osteogenesis and bone homeostasis, from embryonic skeletal development to maintenance of adult bone tissue, by regulating the growth, differentiation, and activity of different cell systems inside and outside the skeleton. Importantly, emerging information from animal studies suggests that targeting miRNAs might become an attractive and new therapeutic approach for osteoporosis or other skeletal diseases, even though there are still major concerns related to potential off target effects and the need of efficient delivery methods in vivo. Moreover, besides their recognized effects at the cellular level, evidence is also gathering that miRNAs are excreted and can circulate in the blood or other body fluids with potential paracrine or endocrine functions. Thus, they could represent suitable candidates for becoming sensitive disease biomarkers in different pathologic conditions, including skeletal disorders. Despite these promising perspectives more work remains to be done until miRNAs can serve as robust therapeutic targets or established diagnostic tools for precision medicine in skeletal disorders.

  17. Analysis of bone protein and mineral composition in bone disease using synchrotron infrared microspectroscopy

    NASA Astrophysics Data System (ADS)

    Miller, Lisa M.; Hamerman, David; Chance, Mark R.; Carlson, Cathy S.

    1999-10-01

    Infrared (IR) microspectroscopy is an analytical technique that is highly sensitive to the chemical components in bone. The brightness of a synchrotron source permits the examination of individual regions of bone in situ at a spatial resolution superior to that of a conventional infrared source. At Beamlines U10B and U2B at the National Synchrotron Light Source, we are examining the role of bone chemical composition in bone disease. In osteoarthritis (OA), it has been demonstrated that the bone underlying the joint cartilage (subchondral bone) becomes thickened prior to cartilage breakdown. Using synchrotron infrared microspectroscopy, we have examined the chemical composition of the subchondral bone in histologically normal and OA monkeys. Results demonstrate that the subchondral bone of OA monkeys is significantly more mineralized than the normal bone, primarily due to an increase in carbonate concentration in the OA bone. High resolution analysis indicates that differences in carbonate content are uniform throughout the subchondral bone region, suggesting that high subchondral bone carbonate may be a marker for OA. Conversely, increases in phosphate content are more pronounced in the region near the marrow space, suggesting that, as the subchondral bone thickens, the bone also becomes more mineralized. Osteoporosis is a disease characterized by a reduction in bone mass and a skeleton that is more susceptible to fracture. To date, it is unclear whether bone remodeled after the onset of osteoporosis differs in chemical composition from older bone. Using fluorescence-assisted infrared microspectroscopy, we are comparing the composition of monkey bone remodeled at various time points after the onset of osteoporosis (induced by ovariectomy). We find that the chemical composition of bone remodeled one year after ovariectomy and one year prior to necropsy is similar to normal bone. On the other hand, bone remodeled two years after ovariectomy is less mature, indicated

  18. Sclerostin and Dickkopf-1 as therapeutic targets in bone diseases.

    PubMed

    Ke, Hua Zhu; Richards, William G; Li, Xiaodong; Ominsky, Michael S

    2012-10-01

    The processes of bone growth, modeling, and remodeling determine the structure, mass, and biomechanical properties of the skeleton. Dysregulated bone resorption or bone formation may lead to metabolic bone diseases. The Wnt pathway plays an important role in bone formation and regeneration, and expression of two Wnt pathway inhibitors, sclerostin and Dickkopf-1 (DKK1), appears to be associated with changes in bone mass. Inactivation of sclerostin leads to substantially increased bone mass in humans and in genetically manipulated animals. Studies in various animal models of bone disease have shown that inhibition of sclerostin using a monoclonal antibody (Scl-Ab) increases bone formation, density, and strength. Additional studies show that Scl-Ab improves bone healing in models of bone repair. Inhibition of DKK1 by monoclonal antibody (DKK1-Ab) stimulates bone formation in younger animals and to a lesser extent in adult animals and enhances fracture healing. Thus, sclerostin and DKK1 are emerging as the leading new targets for anabolic therapies to treat bone diseases such as osteoporosis and for bone repair. Clinical trials are ongoing to evaluate the effects of Scl-Ab and DKK1-Ab in humans for the treatment of bone loss and for bone repair.

  19. [New therapies for children affected by bone diseases].

    PubMed

    Ballhausen, Diana; Dépraz, Nuria Garcia; Kern, Ilse; Unger, Sheila; Bonafé, Luisa

    2012-02-22

    Considerable progress has been achieved in recent years in treating children affected by bone diseases. Advances in the understanding of the molecular pathophysiology of genetic bone diseases have led to the development of enzyme replacement therapies for various lysosomal storage diseases, following the breakthrough initiated in treating Gaucher disease. Clinical studies are underway with tailored molecules correcting bone fragility and alleviating chronic bone pain and other manifestations of hypophosphatasia, or promoting growth of long bones in achondroplasia patients. We further report our very encouraging experience with intravenous bisphosphonate treatment in children suffering from secondary osteopenia and the high prevalence of calcium and vitamin D deficits in these severely disabled children.

  20. Correlation of different bone markers with bone density in patients with rheumatic diseases on glucocorticoid therapy.

    PubMed

    Loddenkemper, Konstanze; Bohl, Nicole; Perka, Carsten; Burmester, Gerd-Rüdiger; Buttgereit, Frank

    2006-02-01

    Osteoporosis is a common concomitant disease in patients with rheumatic diseases on glucocorticoid (GC) therapy. Bone status is usually evaluated by determination of bone density in combination with clinical examinations and laboratory tests. However, the strength of individual biochemical bone makers in GC-induced osteoporosis has yet to be fully clarified. For this reason, different bone markers were investigated in correlation with bone density in patients with rheumatic diseases. Approximately 238 patients (212 women, 26 men) with a rheumatic disease and under GC therapy were examined consecutively for the first time with regard to bone density (BMD) and bone markers [osteocalcin, bone-specific alkaline phosphatase (precipitation method/tandem-MP ostase), crosslinks [pyridinoline (PYD), deoxypyridinoline (DPX), N-terminal telopeptide (NTX)

  1. The Mn-binding proteins of the photosystem II oxygen-evolving complex are decreased in date palms affected by brittle leaf disease.

    PubMed

    Marqués, Jorge; Duran-Vila, Nuria; Daròs, José-Antonio

    2011-04-01

    Brittle leaf disease or maladie des feuilles cassantes (MFC) is a disorder affecting date palms (Phoenix dactylifera L.) which after a long declining process eventually leads to the death of the plant. No causal agent for the disease has been found so far but leaflets of affected palms are Mn-deficient despite the existence of adequate exchangeable Mn in the soils in which affected palms grow. The disease is specifically associated with an increase in a series of chloroplastic RNAs. A proteomic analysis of leaflets of affected and unaffected date palms showed differences in quantities of several proteins. Mn-binding PSBO and PSBP proteins, components of the oxygen-evolving complex of photosystem II, were decreased in affected tissue, reinforcing the relation between MFC and Mn deficiency. The quantities of other proteins were increased by disease suggesting a response to stress.

  2. Mediators of inflammation and bone remodeling in rheumatic disease

    PubMed Central

    Shaw, Anita T.; Gravallese, Ellen M.

    2015-01-01

    Remodeling of bone is a continuous process that occurs throughout life. Under normal physiologic conditions, bone-resorbing osteoclasts and bone-forming osteoblasts are tightly coupled and regulated to ensure the proper balance, such that there is no net change in bone mass. However, inflammation perturbs normal bone homeostasis. The impact of inflammation on bone is dependent upon the anatomic site affected, cell types, factors and cytokines present in the local microenvironment, and local mechanical forces. Cytokines are central to the pathogenesis of inflammation-induced bone loss and contribute to the uncoupling of osteoclast-mediated bone resorption and osteoblast-mediated bone formation, thereby disrupting normal remodeling. In this review, we will discuss the effects of cytokines on bone in two settings, rheumatoid arthritis (RA) and spondyloarthritis (SpA), a disease category that includes ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, inflammatory bowel disease, and juvenile onset spondyloarthropathy. The outcome for bone in these disease settings is quite different, and an understanding of the pathogenic mechanisms leading to the net impact on bone has been essential in developing new therapeutic approaches to bone health in these diseases. PMID:26481971

  3. Enzymatic activities in different strains isolated from healthy and brittle leaf disease affected date palm leaves: study of amylase production conditions.

    PubMed

    Mouna, Jrad; Imen, Fendri; Choba Ines, Ben; Nourredine, Drira; Adel, Kadri; Néji, Gharsallah

    2015-02-01

    The present study aimed to investigate and compare the enzymatic production of endophytic bacteria isolated from healthy and brittle leaf disease affected date palm leaves (pectinase, cellulase, lipase, and amylase). The findings revealed that the enzymatic products from the bacterial isolates of healthy date palm leaves were primarily 33% amylolytic enzyme, 33 % cellulase, 25 % pectinase, and 25 % lipase. The isolates from brittle leaf disease date palm leaves, on the other hand, were noted to produce 16 % amylolytic enzyme, 20 % cellulose, 50 % pectinase, and 50 % lipase. The effects of temperature and pH on amylase, pectinase, and cellulose activities were investigated. The Bacillus subtilis JN934392 strain isolated from healthy date palm leaves produced higher levels of amylase activity at pH 7. A Box Behnken Design (BBD) was employed to optimize amylase extraction. Maximal activity was observed at pH and temperature ranges of pH 6-6.5 and 37-39 °C, respectively. Under those conditions, amylase activity was noted to be attained 9.37 U/ml. The results showed that the enzyme was able to maintain more than 50 % of its activity over a temperature range of 50-80 °C, with an optimum at 70 °C. This bacterial amylase showed high activity compared to other bacteria, which provides support for its promising candidacy for future industrial application.

  4. Re-evaluation of bone pain in patients with type 1 Gaucher disease suggests that bone crises occur in small bones as well as long bones.

    PubMed

    Baris, Hagit N; Weisz Hubshman, Monika; Bar-Sever, Zvi; Kornreich, Liora; Shkalim Zemer, Vered; Cohen, Ian J

    2016-09-01

    Bone crises in type 1 Gaucher disease are reported in long bones and occasionally in weight bearing bones and other bones, but rarely in small bones of the hands and feet. We retrospectively examined the incidence of bone pain in patients followed at the Rabin Medical Center, Israel, before and following the initiation of enzyme replacement therapy (ERT) and evaluated them for bone crises. Of 100 type I Gaucher disease patients, 30 (30%) experienced one or more bone crises. Small bone crises represented 31.5% of all bone crises and were always preceded by crises in other bones. While the incidence of long bone crises reduced after the initiation of ERT, small bone crises increased. Almost 60% of patients with bone crises were of the N370S/84GG genotype suggesting a greater susceptibility of N370S/84GG patients to severe bone complications. These patients also underwent the greatest number of splenectomies (70.6% of splenectomised patients). Splenectomised patients showed a trend towards increased long and small bone crises after surgery. Active investigation of acute pain in the hands and feet in patients in our cohort has revealed a high incidence of small bone crises. Physicians should consider imaging studies to investigate unexplained pain in these areas.

  5. Nanotechnology in the targeted drug delivery for bone diseases and bone regeneration.

    PubMed

    Gu, Wenyi; Wu, Chengtie; Chen, Jiezhong; Xiao, Yin

    2013-01-01

    Nanotechnology is a vigorous research area and one of its important applications is in biomedical sciences. Among biomedical applications, targeted drug delivery is one of the most extensively studied subjects. Nanostructured particles and scaffolds have been widely studied for increasing treatment efficacy and specificity of present treatment approaches. Similarly, this technique has been used for treating bone diseases including bone regeneration. In this review, we have summarized and highlighted the recent advancement of nanostructured particles and scaffolds for the treatment of cancer bone metastasis, osteosarcoma, bone infections and inflammatory diseases, osteoarthritis, as well as for bone regeneration. Nanoparticles used to deliver deoxyribonucleic acid and ribonucleic acid molecules to specific bone sites for gene therapies are also included. The investigation of the implications of nanoparticles in bone diseases have just begun, and has already shown some promising potential. Further studies have to be conducted, aimed specifically at assessing targeted delivery and bioactive scaffolds to further improve their efficacy before they can be used clinically.

  6. Update on Bone Health in Pediatric Chronic Disease.

    PubMed

    Williams, Kristen M

    2016-06-01

    Children and adolescents with chronic disease are predisposed to impaired bone health. Pediatric illness, including type 1 diabetes mellitus, celiac disease, and cystic fibrosis, have significant risk of low bone mineralization and fracture due to underlying inflammation, malabsorption, lack of physical activity, and delayed puberty. Dual-energy x-ray absorptiometry is the primary imaging method to assess bone health in this population. The purpose of this review is to update readers about the assessment and management of bone health in children with common pediatric chronic illnesses and review recent advances in the prevention and treatment of impaired bone health.

  7. 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

  8. Lessons from rare diseases of cartilage and bone.

    PubMed

    Gallagher, James A; Ranganath, Lakshminarayan R; Boyde, Alan

    2015-06-01

    Studying severe phenotypes of rare syndromes can elucidate disease mechanisms of more common disorders and identify potential therapeutic targets. Lessons from rare bone diseases contributed to the development of the most successful class of bone active agents, the bisphosphonates. More recent research on rare bone diseases has helped elucidate key pathways and identify new targets in bone resorption and bone formation including cathepsin K and sclerostin, for which drugs are now in clinical trials. By contrast, there has been much less focus on rare cartilage diseases and osteoarthritis (OA) remains a common disease with no effective therapy. Investigation of rare cartilage syndromes is identifying new potential targets in OA including GDF5 and lubricin. Research on the arthropathy of the ultra-rare disease alkaptonuria has identified several new features of the OA phenotype, including high density mineralized protrusions (HDMPs) which constitute a newly identified mechanism of joint destruction.

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

    PubMed

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

    2013-04-01

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

  10. Gamma images in benign and metabolic bone diseases: volume 1

    SciTech Connect

    Sy, W.M.

    1981-01-01

    Volume 1 of ''Gamma images in benign and metabolic bone diseases'' comprises chapters devoted to: general remarks and considerations, radiopharmaceuticals, Paget disease, osteomyelitis, trauma, benign bone tumors, chronic renal dialysis, acute renal failure, osteomalacia and rickets, and osteoporosis. Although published in 1981, the most recent references in the book were 1978 and most are 1977 or earlier. One of the strongest aspects of the volume are tables which categorize diseases, pathophysiology of disease, and image abnormalities. (JMT)

  11. Optimization of RNA isolation from Brittle Leaf Disease affected date palm leaves and construction of a subtractive cDNA library.

    PubMed

    Saïdi, Mohammed Najib; Gargouri-Bouzid, Radhia; Rayanni, Mariem; Drira, Noureddine

    2009-01-01

    A simple and efficient method was described here for the isolation of high-quality RNA from date palm leaves affected with Brittle Leaf Disease (BLD) and containing high amount of phenolic compounds. The procedure was based on the use of a non-ionic detergent Nonidet-P40 (NP-40), Polyvinylpyrrolidone (PVP), and beta-mercaptoethanol in the extraction buffer in order to isolate cytoplasmic RNA and to prevent the oxidation of phenolic compounds. This method allowed the isolation of intact RNA, suitable for cDNA synthesis and library construction. Differential screening of the subtractive cDNA library from affected leaf RNA led to the identification of some BLD-induced genes.

  12. Enhanced Wnt signaling improves bone mass and strength, but not brittleness, in the Col1a1(+/mov13) mouse model of type I Osteogenesis Imperfecta.

    PubMed

    Jacobsen, Christina M; Schwartz, Marissa A; Roberts, Heather J; Lim, Kyung-Eun; Spevak, Lyudmila; Boskey, Adele L; Zurakowski, David; Robling, Alexander G; Warman, Matthew L

    2016-09-01

    Osteogenesis Imperfecta (OI) comprises a group of genetic skeletal fragility disorders. The mildest form of OI, Osteogenesis Imperfecta type I, is frequently caused by haploinsufficiency mutations in COL1A1, the gene encoding the α1(I) chain of type 1 collagen. Children with OI type I have a 95-fold higher fracture rate compared to unaffected children. Therapies for OI type I in the pediatric population are limited to anti-catabolic agents. In adults with osteoporosis, anabolic therapies that enhance Wnt signaling in bone improve bone mass, and ongoing clinical trials are determining if these therapies also reduce fracture risk. We performed a proof-of-principle experiment in mice to determine whether enhancing Wnt signaling in bone could benefit children with OI type I. We crossed a mouse model of OI type I (Col1a1(+/Mov13)) with a high bone mass (HBM) mouse (Lrp5(+/p.A214V)) that has increased bone strength from enhanced Wnt signaling. Offspring that inherited the OI and HBM alleles had higher bone mass and strength than mice that inherited the OI allele alone. However, OI+HBM and OI mice still had bones with lower ductility compared to wild-type mice. We conclude that enhancing Wnt signaling does not make OI bone normal, but does improve bone properties that could reduce fracture risk. Therefore, agents that enhance Wnt signaling are likely to benefit children and adults with OI type 1.

  13. [Magnesium disorder in metabolic bone diseases].

    PubMed

    Ishii, Akira; Imanishi, Yasuo

    2012-08-01

    Magnesium is abundantly distributed among the body. The half of the magnesium exists in the bone. In addition, magnesium is the second most abundant intracellular cation in vertebrates and essential for maintaining physiological function of the cells. Epidemiologic studies have demonstrated that magnesium deficiency is a risk factor for osteoporosis. The mechanism of bone fragility caused by magnesium deficiency has been intensely studied using animal models of magnesium deficiency. Magnesium deficiency causes decreased osteoblastic function and increased number of osteoclasts. Magnesium deficiency also accelerates mineralization in bone. These observations suggest that disturbed bone metabolic turnover and mineralization causes bone fragility.

  14. The complexity of bone architecture: A tool to differentiate bone diseases

    NASA Astrophysics Data System (ADS)

    Saparin, Peter I.; Gowin, Wolfgang; Kurths, Jürgen; Felsenberg, Dieter

    2000-02-01

    We introduce a generalization of symbolic dynamics to analyze two-dimensional objects and propose measures of complexity to quantify the structure of symbol encoded images. This technique is applied to evaluate the architecture of human cancellous bone by analyzing computed tomography images of vertebrae acquired from specimens and in vivo. The pixels of the preprocessed images are encoded using a mixture of static and dynamic encoding. The architecture of encoded cancellous bone is evaluated as a whole using measures of complexity. A set of new parameters are introduced to quantify the different aspects of structure: complexity and degree of disorder of the architecture as a whole, or spatial arrangements of hard or soft elements of the bone separately. It is found that the complexity of the bone structure relates to its density exponentially. Normal bone has a complex ordered structure, while the architecture during the initial stage of bone loss is characterized by lower complexity and a maximal level of disorder. Increased bone loss leads again to ordered structure, however, its complexity is minimal. This phenomenon was observed in a series of osteoporotic specimens as well as in vivo in patients treated with fluor, and hormone replacement therapy. We found that different bone diseases demonstrate distinctive features captured by the measurements of complexity of the bone's structural composition. It is shown that the application of the proposed technique leads to new insights for understanding of the bone's response on medical treatment and provide important additional information for the diagnostics of bone diseases.

  15. Bone marrow invasion in multiple myeloma and metastatic disease.

    PubMed

    Vilanova, J C; Luna, A

    2016-04-01

    Magnetic resonance imaging (MRI) of the spine is the imaging study of choice for the management of bone marrow disease. MRI sequences enable us to integrate structural and functional information for detecting, staging, and monitoring the response the treatment of multiple myeloma and bone metastases in the spine. Whole-body MRI has been incorporated into different guidelines as the technique of choice for managing multiple myeloma and metastatic bone disease. Normal physiological changes in the yellow and red bone marrow represent a challenge in analyses to differentiate clinically significant findings from those that are not clinically significant. This article describes the findings for normal bone marrow, variants, and invasive processes in multiple myeloma and bone metastases.

  16. Bone Vascularization in Normal and Disease Conditions

    PubMed Central

    Carulli, Christian; Innocenti, Massimo; Brandi, Maria Luisa

    2013-01-01

    Bone vasculature is essential for many processes, such as skeletal development and growth, bone modeling and remodeling, and healing processes. Endothelium is an integral part of bone tissue, expressing a physiological paracrine function via growth factors and chemokines release, and interacting with several cellular lines. Alterations of the complex biochemical interactions between vasculature and bone cells may lead to various clinical manifestations. Two different types of pathologies result: a defect or an excess of bone vasculature or endothelium metabolism. Starting from the molecular basis of the interactions between endothelial and bone cells, the Authors present an overview of the recent acquisitions in the physiopathology of the most important clinical patterns, and the modern therapeutic strategies for their treatments. PMID:23986744

  17. Laser osteoperforation for treatment of inflammatory and destructive bone diseases

    NASA Astrophysics Data System (ADS)

    Privalov, V. A.; Krochek, I. V.; Abushkin, I. A.; Shumilin, I. I.; Lappa, A. V.

    2009-07-01

    The method of laser osteoperforation was developed in experiment and then applied for treatment of 508 patients with osteomyelitis, 51 patients with nonunion and pseudo-joint and 34 patients with different forms of osteochondropathy. The clinical trial proved the efficiency of laser osteoperforation for treatment of both inflammatory and destructive bone diseases. This method is minimally invasive, promotes rapid reduction of bone and soft tissue inflammation, and apparently stimulates bone reparation.

  18. 'Magic bullets' for bone diseases: progress in rational design of bone-seeking medicinal agents.

    PubMed

    Zhang, Sufeng; Gangal, Geeti; Uludağ, Hasan

    2007-03-01

    An ideal therapeutic agent for bone diseases should act solely on bone tissue with no pharmacological activity at other anatomical sites. Current therapeutic agents, however, do not usually display a preferential affinity to bones and non-specifically distribute throughout the body after administration. Attempts to design bone-specific agents have relied on engineering a desired therapeutic agent with bone-seeking molecules so that the latter delivers the therapeutic agents specifically to bones. In this critical review, we summarize the latest attempts to engineer bone-seeking therapeutic agents based on formulating therapeutic agents with bisphosphonates, a class of compounds with high affinity to biological apatite. We first provide a relevant summary of the structure of bone mineral and bisphosphonates, highlighting the mode of interaction between these two entities. The use of bisphosphonates in the diagnosis of bone diseases is then presented, since this application helps us to understand the bone-carrier properties of bisphosphonates under physiological conditions. A summary of recent attempts to formulate bisphosphonates with traditional therapeutic agents to restrict their activities to bone tissues is then provided, with special emphasis on the structure-function relationships of the engineered compounds. Finally, attempts to use bisphosphonates to deliver macromolecular therapeutics (i.e., proteins) are summarized, based on recent data from the authors' lab. The collective research into bone-seeking medicinal agents is progressively laying the foundation for next-generation 'magic bullets' that display desirable activities at the disease sites with no undesirable activity on other organ systems. (164 references.).

  19. Improvement of adynamic bone disease after renal transplantation.

    PubMed

    Abdallah, K A; Jorgetti, V; Pereira, R C; Reis, L M dos; Pereira, L M; Corrêa, P H S; Borelli, A; Ianhez, L E; Moysés, R M A; David-Neto, E

    2006-01-01

    Low bone remodeling and relatively low serum parathyroid hormone (PTH) levels characterize adynamic bone disease (ABD). The impact of renal transplantation (RT) on the course of ABD is unknown. We studied prospectively 13 patients with biopsy-proven ABD after RT. Bone histomorphometry and bone mineral density (BMD) measurements were performed in the 1st and 12th months after RT. Serum PTH, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and osteocalcin were measured regularly throughout the study. Serum PTH levels were slightly elevated at transplantation, normalized at the end of the third month and remained stable thereafter. Bone biopsies performed in the first month after RT revealed low bone turnover in all patients, with positive bone aluminum staining in 5. In the 12th month, second biopsies were performed on 12 patients. Bone histomorphometric dynamic parameters improved in 9 and were completely normalized in 6, whereas no bone mineralization was detected in 3 of these 12 patients. At 12 months post-RT, no bone aluminum was detected in any patient. We also found a decrease in lumbar BMD and an increase in femoral BMD. Patients suffering from ABD, even those with a reduction in PTH levels, may present partial or complete recovery of bone turnover after successful renal transplantation. However, it is not possible to positively identify the mechanisms responsible for the improvement. Identifying these mechanisms should lead to a better understanding of the physiopathology of ABD and to the development of more effective treatments.

  20. Algorithm for employing physical forces in metabolic bone diseases.

    PubMed

    Massari, Leo

    2011-04-01

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

  1. Osteopenia (metabolic bone disease) of prematurity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Osteopenia is defined as postnatal bone mineralization that is inadequate to fully mineralize bones. Osteopenia occurs commonly in very low birth weight (VLBW) infants. Prior to the use of high-mineral containing diets for premature infants, which is the current practice, significant radiographic ch...

  2. Progress in the clinical imaging research of bone diseases on ankle and foot sesamoid bones and accessory ossicles.

    PubMed

    Li, Xiaozhong; Shi, Lenian; Liu, Taiyun; Wang, Lin

    2012-08-01

    Sesamoid bones and accessory ossicles are research focuses of foot and ankle surgery. Pains of the foot and ankle are related to sesamoid bones and accessory ossicles. The specific anatomical and functional relationship of sesamoid bones and accessory ossicles can cause such bone diseases as the dislocation of sesamoid bones and accessory bones, infection, inflammation and necrosis of sesamoid bones, cartilage softening, tenosynovitis of sesamoid bones and the sesamoid bone syndrome. However, these bone diseases are often misdiagnosed or mistreated. In patients with trauma history, relevant diseases of sesamoid bones and accessory ossicles as above mentioned are highly probable to be misdiagnosed as avulsion fractures. In such cases, radiographic findings may provide a basis for clinical diagnosis.

  3. Miscellaneous indications in bone scintigraphy: metabolic bone diseases and malignant bone tumors.

    PubMed

    Cook, Gary J R; Gnanasegaran, Gopinath; Chua, Sue

    2010-01-01

    The diphosphonate bone scan is ideally suited to assess many global, focal or multifocal metabolic bone disorders and there remains a role for conventional bone scintigraphy in metabolic bone disorders at diagnosis, investigation of complications, and treatment response assessment. In contrast, the role of bone scintigraphy in the evaluation of primary malignant bone tumors has reduced with the improvement of morphologic imaging, such as computed tomography and magnetic resonance imaging. However, an increasing role for (18)F-fluorodeoxyglucose positron emission tomography and positron emission tomography/computed tomography is emerging as a functional assessment at diagnosis, staging, and neoadjuvant treatment response assessment.

  4. Homocysteine as a Pathological Biomarker for Bone Disease.

    PubMed

    Behera, Jyotirmaya; Bala, Jyoti; Nuru, Mohammed; Tyagi, Suresh C; Tyagi, Neetu

    2016-11-18

    In the last few decades, perturbation in methyl-group and homocysteine (Hcy) balance have emerged as independent risk factors in a number of pathological conditions including neurodegenerative disease, cardiovascular dysfunction, cancer development, autoimmune disease and kidney disease. Recent studies report Hcy to be a newly recognized risk factor for osteoporosis. Elevated Hcy levels are known to modulate osteoclastgenesis by causing detrimental effects on bone via oxidative stress induced metalloproteinase-mediated extracellular matrix degradation and decrease in bone blood flow. Evidence from previous studies also suggests that the decreased chondrocytes mediated bone mineralization in chick limb-bud mesenchymal cells and during the gestational period of ossification in rat model. However, Hcy imbalance and its role in bone loss, regression in vascular invasion, and osteoporosis, are not clearly understood. More investigations are required to explore the complex interplay between Hcy imbalance and onset of bone disease progression. This article reviews the current body of knowledge on regulation of Hcy mediated oxidative stress and its role in bone remodeling, vascular blood flow and progression of bone disease. This article is protected by copyright. All rights reserved.

  5. Obstructive sleep apnea and metabolic bone disease: Insights in to the relationship between bone and sleep

    PubMed Central

    Swanson, Christine M.; Shea, Steven A.; Stone, Katie L.; Cauley, Jane A.; Rosen, Clifford J.; Redline, Susan; Karsenty, Gerard; Orwoll, Eric S.

    2015-01-01

    Obstructive sleep apnea (OSA) and low bone mass are two prevalent conditions, particularly among older adults, a section of the U.S. population that is expected to grow dramatically over the coming years. OSA, the most common form of sleep disordered breathing, has been linked to multiple cardiovascular, metabolic, hormonal and inflammatory derangements and may have adverse effects on bone. However, little is known about how OSA (including the associated hypoxia and sleep loss) affects bone metabolism. In order to gain insight into the relationship between sleep and bone, we review the growing information on OSA and metabolic bone disease and discuss the pathophysiological mechanisms by which OSA may affect bone metabolism/architecture. PMID:25639209

  6. Bone Marrow Diseases - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Bone Marrow Diseases URL of this page: https://medlineplus.gov/languages/bonemarrowdiseases.html Other topics A-Z A B ...

  7. Fluoride-related bone disease associated with habitual tea consumption.

    PubMed

    Hallanger Johnson, Julie E; Kearns, Ann E; Doran, Patric M; Khoo, Teck Kim; Wermers, Robert A

    2007-06-01

    Acquired osteosclerosis is a rare disorder of bone formation but an important consideration in adults with sclerotic bones or elevated bone density results. In such patients, malignancy, hepatitis C, and fluorosis should all be considered when making a diagnosis. We describe 4 patients evaluated at our Metabolic Bone Disease Clinic from May 1, 1997, to July 1, 2006, whose bone disorders resulted from chronic fluoride exposure due to excessive tea intake. Three of these patients had toxic serum fluoride levels (> 15 micromol/L). Although the clinical presentation of the patients varied, all 4 had an unexpectedly elevated spine bone mineral density that was proportionately higher than the bone mineral density at the hip. Other clinical features included gastrointestinal symptoms such as nausea, vomiting, and weight loss; lower extremity pain sometimes associated with stress fractures of the lower extremities; renal insufficiency; and elevated alkaline phosphatase levels. Readily available, tea often contains high levels of fluoride. Obsessive-compulsive drinking behaviors and renal insufficiency may predispose to excessive fluoride consumption and accumulation. The current cases show that fluoride-related bone disease is an important clinical consideration in patients with dense bones or gastrointestinal symptoms and a history of excessive tea consumption. Furthermore, fluoride excess should be considered in all patients with a history of excessive tea consumption, especially due to its insidious nature and nonspecific clinical presentation.

  8. Biochemical markers of bone turnover for the clinical assessment of metabolic bone disease.

    PubMed

    Delmas, P D

    1990-03-01

    There is not yet an ideal marker of bone formation, but circulating BGP is the most satisfactory at present. New developments include the use of sheep BGP64 and human BGP85 as an immunogen and monoclonal antibodies, which may recognize fragments of BGP released during resorption. The specific measurement of bone alkaline phosphatase and the assay of procollagen fragments and of other noncollagenous bone-related proteins will allow a more precise assessment of the complex osteoblastic functions in normal and pathologic conditions. Finding a sensitive and specific marker of resorption is a challenge because all constituents of bone matrix are likely to be degraded into minute peptides during osteoclastic bone resorption. The measurement of pyridinium crosslinks and possibly of tartrate-resistant acid phosphate by a bone-specific monoclonal antibody are the most tangible improvements in this area. These markers need to be validated by comparison with data obtained by direct measurement of bone turnover on iliac crest biopsy. It should be remembered, however, that circulating markers reflect the overall activity of the whole skeleton, including the cortical, subcortical, and trabecular envelopes, which have different remodeling rates in normal and abnormal states. A circulating marker will not detect a specific defect of the cellular activity of one compartment of bone if the summated turnover of the skeleton is unchanged. Conversely, bone histomorphometry is limited to a small area of the trabecular envelope but allows detection of a specific defect at the cellular level. These differences should be kept in mind, as there is growing evidence that, for example, bone mass and bone turnover of osteoporotic patients before and during treatment vary in different appendicular/axial and cortical/trabecular compartments. Finally, a single marker might be valuable in some diseases and not in others (such as serum BGP in Paget's disease of bone). Despite these difficulties

  9. Novel therapies in benign and malignant bone diseases.

    PubMed

    Rachner, Tilman D; Hadji, Peyman; Hofbauer, Lorenz C

    2012-06-01

    With an ageing population and improving cancer therapies, the two most common benign and malignant bone diseases, osteoporosis and bone metastases, will continue to affect an increasing number of patients. Our expanding knowledge of the molecular processes underlying these conditions has resulted in novel bone targets that are currently being explored in clinical trials. Clearly, the approval of denosumab, a monoclonal antibody directed against RANKL, has just marked the beginning of a new era for bone therapy with several additional new therapies lining up for clinical approval in the coming years. Potential agents targeting the osteoclast include cathepsin K, currently in phase 3 trials, and src inhibitors. Amongst anabolic agents, inhibitors of the Wnt-inhibitor sclerostin and dickkopf-1 are promising in clinical trials. Here, we will provide a comprehensive overview of the most promising agents currently explored for the treatment of bone diseases.

  10. Bone health and associated metabolic complications in neuromuscular diseases.

    PubMed

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

    2012-11-01

    This article reviews the recent literature regarding bone health as it relates to the patient living with neuromuscular disease (NMD). Studies defining the scope of bone-related disease in NMD are scant. The available evidence is discussed, focusing on abnormal calcium metabolism, increased fracture risk, and the prevalence of both scoliosis and hypovitaminosis D in Duchenne muscular dystrophy, amyotrophic lateral sclerosis, and spinal muscular atrophy. Future directions are discussed, including the urgent need for studies both to determine the nature and extent of poor bone health, and to evaluate the therapeutic effect of available osteoporosis treatments in patients with NMD.

  11. [Cosmetology and brittle nails].

    PubMed

    Abimelec, P

    2000-12-15

    The knowledge of manicure techniques and nail cosmetics compositions are a prerequisite to the understanding of their potential side effects. The brittle nail syndrome is a common problem that roughly affect 20% of women. We will review the etiologic hypothesis, describe the various presentations, and suggest a treatment for this perplexing problem.

  12. Brittleness of ceramics

    NASA Technical Reports Server (NTRS)

    Kroupa, F.

    1984-01-01

    The main characteristics of mechanical properties of ceramics are summarized and the causes of their brittleness, especially the limited mobility of dislocations, are discussed. The possibility of improving the fracture toughness of ceramics and the basic research needs relating to technology, structure and mechanical properties of ceramics are stressed in connection with their possible applications in engineering at high temperature.

  13. Paget’s disease of bone: an osteoimmunological disorder?

    PubMed Central

    Numan, Mohamed S; Amiable, Nathalie; Brown, Jacques P; Michou, Laëtitia

    2015-01-01

    Osteoimmunology represents a large area of research resulting from the cross talk between bone and immune systems. Many cytokines and signaling cascades are involved in the field of osteoimmunology, originating from various cell types. The RANK/receptor activator of nuclear factor Kappa-B ligand (RANKL)/osteoprotegerin (OPG) signaling has a pivotal role in osteoimmunology, in addition to proinflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1, IL-6, and IL-17. Clinically, osteoimmunological disorders, such as rheumatoid arthritis, osteoporosis, and periodontitis, should be classified according to their pattern of osteoimmunological serum biomarkers. Paget’s disease of bone is a common metabolic bone disorder, resulting from an excessively increased bone resorption coupled with aberrant bone formation. With the exception of the cellular responses to measles virus nucleocapsid protein and the interferon-gamma signature, the exact role of the immune system in Paget’s disease of bone is not well understood. The cytokine profiles, such as the increased levels of IL-6 and the interferon-gamma signature observed in this disease, are also very similar to those observed in other osteoimmunological disorders. As a potential osteoimmunological disorder, the treatment of Paget’s disease of bone may also benefit from progress made in targeted therapies, in particular for receptor activator of nuclear factor Kappa-B ligand and IL-6 signaling inhibition. PMID:26316708

  14. Zoledronic acid in the management of metastatic bone disease.

    PubMed

    Santini, Daniele; Fratto, Maria Elisabetta; Vincenzi, Bruno; Galluzzo, Sara; Tonini, Giuseppe

    2006-12-01

    Bisphosphonate therapy has become a standard of therapy for patients with malignant bone disease. Moreover, in vivo preclinical and preliminary clinical data suggest that bisphosphonates may prevent cancer treatment-induced bone loss and the onset of malignant bone disease in patients with early-stage cancer. This comprehensive review critically reports the several preclinical evidences of action of bisphosphonates on osteoclasts, lymphocytes and tumour cells. In addition, all the clinical trials evaluating the effects of principal bisphosphonates on skeletal disease progression in patients with breast cancer, prostate cancer, non-small cell lung cancer and other cancers have been reported. Of the available bisphosphonates, intravenous zoledronic acid has demonstrated the broadest clinical activity and is actually approved for the treatment of bone metastases from any solid tumour in many countries. Renal safety is an important consideration for oncologists who are treating patients with bisphosphonates. This issue and the other topics relating to the safety of bisphosphonates are discussed in this review.

  15. Diabetes mellitus and bone disease in cystic fibrosis.

    PubMed

    Curran, David R; McArdle, John R; Talwalkar, Jaideep S

    2009-10-01

    Patients with cystic fibrosis are frequently affected with pancreatic insufficiency and are predisposed to the development of diabetes mellitus (DM) and bone demineralization. Cystic fibrosis-related diabetes mellitus is a clinical entity distinct from type 1 and type 2 diabetes, with important implications for the nutritional and pulmonary health of cystic fibrosis patients. This form of diabetes owes largely to insulin deficiency, but alterations in insulin sensitivity and hepatic glucose production have also been described. Therapy for cystic fibrosis-related diabetes differs substantially from type 2 DM, with careful attention to prandial glycemic excursions crucial to controlling its metabolic effects. Bone disease, including osteopenia and osteoporosis, also occurs with increased frequency in cystic fibrosis, owing to defects in intestinal absorption, chronic inflammation, lung disease, low body weight, and gonadal dysfunction. The pathogenesis, implications, diagnosis, and therapy of cystic fibrosis-related bone demineralization are discussed, with attention to recommended approaches to prevention of and treatment of established bone disease.

  16. Imaging Paget's disease of bone--from head to toe.

    PubMed

    Cortis, K; Micallef, K; Mizzi, A

    2011-07-01

    Paget's disease of the bone is a common, non-inflammatory, metabolic, skeletal disorder of unknown aetiology characterized by an increase in osteoclast-mediated bone resorption and compensatory excessive osteoblast activation. Prevalence increases with age, and a pronounced geographical variation is well documented. The disease is often an incidental finding on a radiological examination requested for an unrelated indication. The osteolytic, mixed osteolytic/osteoblastic, and osteosclerotic phases may occur in the same patient and same bone in a synchronous or metachronous fashion. Radiological features in each phase mirror the histopathological appearances, and are distinctive enough to establish a diagnosis with confidence. Using multi-technique imaging, this review illustrates the most common and the not so common radiological patterns of involvement in Paget's disease of bone observed at our centre during the past 20 years.

  17. Bone Material Properties in Osteogenesis Imperfecta.

    PubMed

    Bishop, Nick

    2016-04-01

    Osteogenesis imperfecta entrains changes at every level in bone tissue, from the disorganization of the collagen molecules and mineral platelets within and between collagen fibrils to the macroarchitecture of the whole skeleton. Investigations using an array of sophisticated instruments at multiple scale levels have now determined many aspects of the effect of the disease on the material properties of bone tissue. The brittle nature of bone in osteogenesis imperfecta reflects both increased bone mineralization density-the quantity of mineral in relation to the quantity of matrix within a specific bone volume-and altered matrix-matrix and matrix mineral interactions. Contributions to fracture resistance at multiple scale lengths are discussed, comparing normal and brittle bone. Integrating the available information provides both a better understanding of the effect of current approaches to treatment-largely improved architecture and possibly some macroscale toughening-and indicates potential opportunities for alternative strategies that can influence fracture resistance at longer-length scales.

  18. Prediction and Informative Risk Factor Selection of Bone Diseases.

    PubMed

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

    2015-01-01

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

  19. [Pathological and metabolic bone diseases: Clinical importance for fracture treatment].

    PubMed

    Oheim, R

    2015-12-01

    Pathological and metabolic bone diseases are common and relevant occurrences in orthopedics and trauma surgery; however, fractures are often treated as being the illness itself and not seen as the symptom of an underlying bone disease. This is why further diagnostics and systemic treatment options are often insufficiently considered in the routine treatment of fractures. This review focuses on osteoporosis, osteopetrosis, hypophosphatasia and Paget's disease of bone.In patients with osteoporotic vertebral or proximal femur fractures, pharmaceutical treatment to prevent subsequent fractures is an integral part of fracture therapy together with surgical treatment. Osteopetrosis is caused by compromised osteoclastic bone resorption; therefore, even in the face of an elevated bone mass, vitamin D3 supplementation is crucial to avoid clinically relevant hypocalcemia. Unspecific symptoms of the musculoskeletal system, especially together with stress fractures, are typically found in patients suffering from hypophosphatasia. In these patients measurement of alkaline phosphatase shows reduced enzyme activity. Elevated levels of alkaline phosphatase are found in Paget's disease of bone where bisphosphonates are still the treatment of choice.

  20. Corrugation of the skull in Paget's disease of bone.

    PubMed Central

    Chakravorty, N. K.; Das, S. K.; Kataria, M. S.

    1977-01-01

    Paget's disease of bone has been known for about 100 years and the usual deformities of bone, e.g. bowed tibia, large head, are well described in medical text books. However, there does not appear to have been a description of corrugation of the skull as a recognized deformity in Paget's disease. Three cases are now described to illustrate this deformity as an unusual but valuable sign in this disease. Images Fig. 5 Fig. 6 Fig. 1 Fig. 2 Fig. 3 Fig. 4 Figs. 7 and 8 PMID:876912

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

    PubMed

    Kanazawa, Ippei; Sugimoto, Toshitsugu

    2013-11-01

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

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

    PubMed

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

    2014-09-01

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

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

    PubMed

    Hamed, Sherifa A

    2016-01-01

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

  4. [Cat-scratch disease with bone compromise: atypical manifestation].

    PubMed

    Rodríguez C, Magdalena; Giachetto L, Gustavo; Cuneo E, Alejandro; Gutiérrez B, María del C; Shimchack R, Mario; Pírez G, M Catalina

    2009-08-01

    Fever, headache, myalgias and lymphadenopathy are characteristic manifestations of cat-scratch disease but other less common findings are described in 2 to 10% of cases. We report two children that presented with hepatosplenic abscesses and bone involvement. One child, had multiple areas of increased uptake in the bone scintigram with a positive serology (IgG > 1/256, IgM slightly positive). The second child had destruction of the L2 vertebral body that compromised the channel and right foramen as visualized by MRI. In both cases, bacilli were observed in the bone biopsy by Warthing-Starry stain.

  5. Leptin in joint and bone diseases: new insights.

    PubMed

    Scotece, M; Conde, J; Lopez, V; Lago, F; Pino, J; Gomez-Reino, J J; Gualillo, O

    2013-01-01

    Leptin is an adipokine with pleiotropic actions that regulates food intake, energy metabolism, inflammation and immunity, and also participates in the complex mechanism that regulates skeleton biology, both at bone and cartilage level. Leptin is increased in obesity and contributes to the "low-grade inflammatory state" of obese subjects causing a cluster of metabolic aberrations that affects joints and bone. In this review, we report the most recent research advances about the role of leptin in bone and cartilage function and its implication in inflammatory and degenerative joint diseases, such as osteoarthritis, rheumatoid arthritis and osteoporosis.

  6. Proceedings of the 2015 Santa Fe Bone Symposium: Clinical Applications of Scientific Advances in Osteoporosis and Metabolic Bone Disease.

    PubMed

    Lewiecki, E Michael; Baron, Roland; Bilezikian, John P; Gagel, Robert E; Leonard, Mary B; Leslie, William D; McClung, Michael R; Miller, Paul D

    2016-01-01

    The 2015 Santa Fe Bone Symposium was a venue for healthcare professionals and clinical researchers to present and discuss the clinical relevance of recent advances in the science of skeletal disorders, with a focus on osteoporosis and metabolic bone disease. Symposium topics included new developments in the translation of basic bone science to improved patient care, osteoporosis treatment duration, pediatric bone disease, update of fracture risk assessment, cancer treatment-related bone loss, fracture liaison services, a review of the most significant studies of the past year, and the use of telementoring with Bone Health Extension for Community Healthcare Outcomes, a force multiplier to improve the care of osteoporosis in underserved communities.

  7. Adipokines as drug targets in joint and bone disease.

    PubMed

    Scotece, Morena; Conde, Javier; Vuolteenaho, Katriina; Koskinen, Anna; López, Veronica; Gómez-Reino, Juan; Lago, Francisca; Moilanen, Eeva; Gualillo, Oreste

    2014-03-01

    White adipose tissue is now recognized to be a multifactorial organ secreting several adipose-derived factors that have been collectively termed 'adipokines'. Adipokines are pleiotropic molecules that contribute to the so-called 'low-grade inflammatory state' of obese subjects creating a cluster of metabolic aberrations including autoimmune and inflammatory diseases that affect joints and bone. The aim of this review is to present knowledge about the role of adipokines in bone and cartilage function, as well as in inflammatory and degenerative joint disease. We discuss clinical implications and then survey attempts to exploit this role for therapeutic gain, which holds potential as a novel approach for drug development in bone and joint disease.

  8. Biochemical markers in the assessment of bone disease

    NASA Technical Reports Server (NTRS)

    Bikle, D. D.

    1997-01-01

    As the mean age of our population increases, increasing attention has been paid to the diseases associated with aging, including diseases of the skeleton such as osteoporosis. Effective means of treating and possibly preventing such skeletal disorders are emerging, making their early recognition an important goal for the primary care physician. Although bone density measurements and skeletal imaging studies remain of primary diagnostic importance in this regard, a large number of assays for biochemical markers of bone formation and resorption are being developed that promise to complement the densitometry measurements and imaging studies, providing an assessment of the rates of bone turnover and an earlier evaluation of the effects of therapy. In this review, emphasizing the recent literature, the major biochemical markers currently in use or under active investigation are described, and their application in a number of diseases of the skeleton including osteoporosis is evaluated.

  9. Bone scintigraphy in Ollier's disease: A rare case report

    PubMed Central

    Khan, Shoukat H; Rather, Tanveer A; Koul, Parvaiz A; Makhdoomi, Rumana; Bhat, Abdul Rashid; Malik, Dharmender; Manohar, Ram

    2013-01-01

    Ollier's disease is characterized by multiple skeletal enchondroma. There are published data regarding Ollier's disease being associated with vascular malformations and non-skeletal neoplasms. We report a case of Ollier's disease in a young male associated with osteochondroma, low grade glioma in the insular cortex of brain and Gilbert's syndrome. Technetium-99m methylene diphosphonate whole body bone scan is a sensitive investigation to ascertain the complete extent of skeletal involvement particularly the asymptomatic sites. PMID:24379533

  10. Rare Bone Diseases and Their Dental, Oral, and Craniofacial Manifestations

    PubMed Central

    Foster, B.L.; Ramnitz, M.S.; Gafni, R.I.; Burke, A.B.; Boyce, A.M.; Lee, J.S.; Wright, J.T.; Akintoye, S.O.; Somerman, M.J.; Collins, M.T.

    2014-01-01

    Hereditary diseases affecting the skeleton are heterogeneous in etiology and severity. Though many of these conditions are individually rare, the total number of people affected is great. These disorders often include dental-oral-craniofacial (DOC) manifestations, but the combination of the rarity and lack of in-depth reporting often limit our understanding and ability to diagnose and treat affected individuals. In this review, we focus on dental, oral, and craniofacial manifestations of rare bone diseases. Discussed are defects in 4 key physiologic processes in bone/tooth formation that serve as models for the understanding of other diseases in the skeleton and DOC complex: progenitor cell differentiation (fibrous dysplasia), extracellular matrix production (osteogenesis imperfecta), mineralization (familial tumoral calcinosis/hyperostosis hyperphosphatemia syndrome, hypophosphatemic rickets, and hypophosphatasia), and bone resorption (Gorham-Stout disease). For each condition, we highlight causative mutations (when known), etiopathology in the skeleton and DOC complex, and treatments. By understanding how these 4 foci are subverted to cause disease, we aim to improve the identification of genetic, molecular, and/or biologic causes, diagnoses, and treatment of these and other rare bone conditions that may share underlying mechanisms of disease. PMID:24700690

  11. Rare bone diseases and their dental, oral, and craniofacial manifestations.

    PubMed

    Foster, B L; Ramnitz, M S; Gafni, R I; Burke, A B; Boyce, A M; Lee, J S; Wright, J T; Akintoye, S O; Somerman, M J; Collins, M T

    2014-07-01

    Hereditary diseases affecting the skeleton are heterogeneous in etiology and severity. Though many of these conditions are individually rare, the total number of people affected is great. These disorders often include dental-oral-craniofacial (DOC) manifestations, but the combination of the rarity and lack of in-depth reporting often limit our understanding and ability to diagnose and treat affected individuals. In this review, we focus on dental, oral, and craniofacial manifestations of rare bone diseases. Discussed are defects in 4 key physiologic processes in bone/tooth formation that serve as models for the understanding of other diseases in the skeleton and DOC complex: progenitor cell differentiation (fibrous dysplasia), extracellular matrix production (osteogenesis imperfecta), mineralization (familial tumoral calcinosis/hyperostosis hyperphosphatemia syndrome, hypophosphatemic rickets, and hypophosphatasia), and bone resorption (Gorham-Stout disease). For each condition, we highlight causative mutations (when known), etiopathology in the skeleton and DOC complex, and treatments. By understanding how these 4 foci are subverted to cause disease, we aim to improve the identification of genetic, molecular, and/or biologic causes, diagnoses, and treatment of these and other rare bone conditions that may share underlying mechanisms of disease.

  12. Three-phase bone scintigraphy in Pellegrini-Stieda disease.

    PubMed

    Liu, R S; Chou, C S; Yeh, S H

    1987-01-01

    In a patient with Pellegrini-Stieda disease, radiographs of the knees were unremarkable at the time the three-phase bone scintigraphy was abnormal. The results of follow-up radiographs three months later remained normal in the left knee, where local steroid injection was given, but revealed typical positive results in the right knee with no treatment. The three-phase bone scintigraphic pattern is rather typical and antedates the radiographic changes. Thus, the radionuclide technique would provide a useful procedure for the early diagnosis and treatment of Pellegrini-Stieda disease.

  13. Multiple 'Brown Tumors' Masquerading as Metastatic Bone Disease.

    PubMed

    Vaishya, Raju; Agarwal, Amit Kumar; Singh, Harsh; Vijay, Vipul

    2015-12-23

    'Brown tumors' are known as 'osteitis fibrosa cystica' or 'Von Recklinghausen's disease' of the bone. A high index of suspicion is required by the treating doctor for diagnosing a 'brown tumor' in its early stage. Clinical suspicion, along with laboratory and radiological investigations, is required to diagnose this condition. We present a case of a 65-year-old woman who had multiple bony lesions and a thyroid nodule, which was initially considered as a metastatic bone disease, but later turned out to be 'brown tumors.' In all cases with multiple osteolytic lesions, a possibility of 'brown tumor' must be kept in mind.

  14. Metabolic bone diseases during long-term total parenteral nutrition.

    PubMed

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

    2007-01-01

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

  15. Metabolic Bone Disease in Viral Cirrhosis: A Prospective Study

    PubMed Central

    Goubraim, Rabia; Kabbaj, Nawal; Salihoun, Mouna; Chaoui, Zakia; Nya, M'Hamed; Amrani, Naima

    2013-01-01

    Background/Aim. Metabolic Bone disorders are well-recognized extrahepatic complications of cirrhosis. The aim was to report their prevalence and the associated factors to their development in patients with viral cirrhosis. Patients and Methods. All consecutive patients with viral cirrhosis were prospectively enrolled. Parathyroid hormone, 25-hydroxyvitamin D, liver function, and phosphocalcic tests were measured in all patients. Bone mineral density was measured at the lumbar spine and total hip by dual-energy X-ray absorptiometry. Data were analyzed using SPSS software. Results. Forty-six cirrhotic patients were included with hepatitis C (87%) and hepatitis B (13%). The Child-Pugh score was grade A in 87% of cases and grade B in 13%. Thirty-seven patients had decreased bone mineral density with osteopenia in 24 patients and osteoporosis in 13 patients. Decreased 25-hydroxyvitamin D was found in 95.6% of cases. Bone disorders were significantly more frequent in old patients with low body mass index, long duration of liver disease, and low 25-hydroxyvitamin D level. None of these factors was an independent factor associated with bone disorders. Conclusion. Our study revealed a high prevalence of metabolic bone disorders among viral cirrhotic patients. Consequently, bone mineral density assessment should be performed systematically in all cirrhotic patients. PMID:27398385

  16. [Bone disease with Pain. Colles' fracture].

    PubMed

    Yajima, Hiroshi

    2008-11-01

    The distal radius is one of the most commonly fractured long bone. Colles' fracture results from a fall on the dorsiflexed and pronated hand. The dinner-fork deformity is the typical deformity of the Colles' fracture. For patients with no or a little displacement, conservative treatment is applied. The non-bridge type external fixator is applied for patients without an intra articular fracture. For patients with a comminuted fracture, the locking plate (volar approach) is recommended. During the healing period, shoulder, elbow and finger exercise should be insisted.

  17. How Is Paget's Disease of Bone Diagnosed?

    MedlinePlus

    ... than-usual level of a chemical substance called serum alkaline phosphatase (SAP), it is a sign that the disease may be present. SAP is a type of ... than twice the usual level strongly suggests Paget’s disease, especially if the person’s serum calcium level, phosphorus level, and kidney function are ...

  18. [Diet for lifestyle-related diseases to maintain bone health].

    PubMed

    Hirota, Takako; Hirota, Kenji

    2011-05-01

    Dieting methods for preventing age-related diseases such as cardiovascular disease, hypertension and diabetes, as well as osteoporosis are proposed here. Losing weight to prevent and ameliorate metabolic syndrome can lead to loss of bone and muscle mass. However, when subjects had milk before dinner while dieting, their fat mass was efficiently decreased and their muscle mass increased without any change of bone mass. Increased intake of vitamin D enhanced these effects. Therefore we suggest that people with high risk of metabolic disorders should take more low fat dairy products and fish, together with fruits, vegetables, and soy in order to increase their intake of calcium, vitamin D, n-3 polyunsaturated fatty acids, protein, antioxidants, various vitamins and minerals, and fiber to protect them from the deterioration of arteries and bones.

  19. Fungal Root Microbiome from Healthy and Brittle Leaf Diseased Date Palm Trees (Phoenix dactylifera L.) Reveals a Hidden Untapped Arsenal of Antibacterial and Broad Spectrum Antifungal Secondary Metabolites.

    PubMed

    Mefteh, Fedia B; Daoud, Amal; Chenari Bouket, Ali; Alenezi, Faizah N; Luptakova, Lenka; Rateb, Mostafa E; Kadri, Adel; Gharsallah, Neji; Belbahri, Lassaad

    2017-01-01

    In this study, we aimed to explore and compare the composition, metabolic diversity and antimicrobial potential of endophytic fungi colonizing internal tissues of healthy and brittle leaf diseased (BLD) date palm trees (Phoenix dactylifera L.) widely cultivated in arid zones of Tunisia. A total of 52 endophytic fungi were isolated from healthy and BLD roots of date palm trees, identified based on internal transcribed spacer-rDNA sequence analysis and shown to represent 13 species belonging to five genera. About 36.8% of isolates were shared between healthy and diseased root fungal microbiomes, whereas 18.4 and 44.7% of isolates were specific to healthy and BLD root fungal microbiomes, respectively. All isolates were able to produce at least two of the screened enzymes including amylase, cellulase, chitinase, pectinase, protease, laccase and lipase. A preliminary screening of the isolates using disk diffusion method for antibacterial activity against four Gram-positive and three Gram-negative bacteria and antifungal activities against three phytopathogenic fungi indicated that healthy and BLD root fungal microbiomes displayed interesting bioactivities against examined bacteria and broad spectrum bioactivity against fungal pathogens. Some of these endophytic fungi (17 isolates) were fermented and their extracts were evaluated for antimicrobial potential against bacterial and fungal isolates. Results revealed that fungal extracts exhibited antibacterial activities and were responsible for approximately half of antifungal activities against living fungi. These results suggest a strong link between fungal bioactivities and their secondary metabolite arsenal. EtOAc extracts of Geotrichum candidum and Thielaviopsis punctulata originating from BLD microbiome gave best results against Micrococcus luteus and Bacillus subtilis with minimum inhibitory concentration (MIC, 0.78 mg/mL) and minimum bactericidal concentration (6.25 mg/mL). G. candidum gave the best result against

  20. Fungal Root Microbiome from Healthy and Brittle Leaf Diseased Date Palm Trees (Phoenix dactylifera L.) Reveals a Hidden Untapped Arsenal of Antibacterial and Broad Spectrum Antifungal Secondary Metabolites

    PubMed Central

    Mefteh, Fedia B.; Daoud, Amal; Chenari Bouket, Ali; Alenezi, Faizah N.; Luptakova, Lenka; Rateb, Mostafa E.; Kadri, Adel; Gharsallah, Neji; Belbahri, Lassaad

    2017-01-01

    In this study, we aimed to explore and compare the composition, metabolic diversity and antimicrobial potential of endophytic fungi colonizing internal tissues of healthy and brittle leaf diseased (BLD) date palm trees (Phoenix dactylifera L.) widely cultivated in arid zones of Tunisia. A total of 52 endophytic fungi were isolated from healthy and BLD roots of date palm trees, identified based on internal transcribed spacer-rDNA sequence analysis and shown to represent 13 species belonging to five genera. About 36.8% of isolates were shared between healthy and diseased root fungal microbiomes, whereas 18.4 and 44.7% of isolates were specific to healthy and BLD root fungal microbiomes, respectively. All isolates were able to produce at least two of the screened enzymes including amylase, cellulase, chitinase, pectinase, protease, laccase and lipase. A preliminary screening of the isolates using disk diffusion method for antibacterial activity against four Gram-positive and three Gram-negative bacteria and antifungal activities against three phytopathogenic fungi indicated that healthy and BLD root fungal microbiomes displayed interesting bioactivities against examined bacteria and broad spectrum bioactivity against fungal pathogens. Some of these endophytic fungi (17 isolates) were fermented and their extracts were evaluated for antimicrobial potential against bacterial and fungal isolates. Results revealed that fungal extracts exhibited antibacterial activities and were responsible for approximately half of antifungal activities against living fungi. These results suggest a strong link between fungal bioactivities and their secondary metabolite arsenal. EtOAc extracts of Geotrichum candidum and Thielaviopsis punctulata originating from BLD microbiome gave best results against Micrococcus luteus and Bacillus subtilis with minimum inhibitory concentration (MIC, 0.78 mg/mL) and minimum bactericidal concentration (6.25 mg/mL). G. candidum gave the best result against

  1. Gaucher disease: the role of the specialist on metabolic bone diseases.

    PubMed

    Masi, Laura; Brandi, Maria Luisa

    2015-01-01

    According to European legislation, a disease can be considered rare or "orphan" when it affects less than 1 subject of 2000 (1). Often these diseases affecting the pediatric age, are complex diseases and chronically debilitating and for this motive need the intervention of multidisciplinary skills specific. Among the rare disease as affecting the skeleton more than 400 are characterized by dysplastic changes of the skeleton (2). Alongside the disorders affecting the skeleton primitively, many systemic diseases can have a bone involvement. Among these, the Gaucher disease (GD), an heterogeneous lysosomal storage determined by hereditary enzyme deficiency of β-glucosidase. Patients with this disease have skeletal disorders of varying severity (Erlenmeyer flask deformity, lytic lesions and osteonecrosis, pathological fractures) that affects both the bone marrow, both mineralized bone with progressive damage of the tissue. The bone disease is the most debilitating of GD and can have a significant impact on the quality of life of patients. Thorough evaluations by monitoring biochemical markers of bone turnover and instrumental, with a quantitative and qualitative evaluation of the bone, are of fundamental importance to intervene early so they can prevent complications irreversible.

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

    PubMed

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

    2015-01-01

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

  3. In vivo bone aluminum measurements in patients with renal disease

    SciTech Connect

    Ellis, K.J.; Kelleher, S.P.

    1986-01-01

    Contamination of the dialysis solution with trace amounts of aluminum and long-term use of aluminum-based phosphate binders have led to increased body burden of aluminum in patients with end-stage renal disease. A significant clinical problem associated with aluminum-overload is the early diagnosis of aluminum-induced dialysis dementia and osteomalacic osteodystrophy. There are few, if any, blood or urine indices that provide an early monitor of this bone disease, especially in the asymptomatic patient. Although a bone biopsy is usually the basis for the final clinical diagnosis, this procedure is not recommended for routine monitoring of patients. The present technique demonstrates the direct in vivo measurement of bone aluminum levels in patients with renal failure. The interference normally present from activation of bone phosphorus is eliminated by using a thermal/epithermal neutron beam. For the clinical management of the patients, the Al/Ca ratio for the hand may be more useful than an absolute measurement of the total body or skeletal aluminum burden. The relationship between the increased serum Al levels following disferrioxamine infusion and the direct in vivo measurement of bone aluminum using the Al/Ca ratio are currently under investigation. The neutron activation procedure presented in this pilot study is a promising new technique with an immediate clinical application. 5 refs., 3 figs., 1 tab.

  4. Bone Disease in the Common Marmoset: Radiographic and Histological Findings.

    PubMed

    Olson, E J; Shaw, G C; Hutchinson, E K; Schultz-Darken, N; Bolton, I D; Parker, J B; Morrison, J M; Baxter, V K; Pate, K A Metcalf; Mankowski, J L; Carlson, C S

    2015-09-01

    The common marmoset (Callithrix jacchus) is a New World primate that is used in biomedical research due to its small size and relative ease of handling compared with larger primates. Although bone disease in common marmosets is well recognized, there are very few detailed descriptions in the literature that cover the range of lesions seen in these animals. For all animals used to model human disease, it is important to be aware of background lesions that may affect the interpretation of study findings. This retrospective study details bone diseases encountered in marmoset breeding colonies at 2 different institutions. Affected marmosets at Johns Hopkins University had lesions compatible with diagnoses of rickets, fibrous osteodystrophy and osteopenia. Affected marmosets at the Wisconsin National Primate Research Center exhibited severe lesions of osteoclastic bone resorption and remodeling that had an unusual distribution and were not easily categorized into a known disease entity. The purpose of this report is to document these naturally occurring skeletal lesions of common marmosets and suggest an approach to evaluating skeletal disease in prospective studies of these animals that will allow the most accurate diagnoses.

  5. Role of Bone Biopsy in Stages 3 to 4 Chronic Kidney Disease

    PubMed Central

    Gal-Moscovici, Anca; Sprague, Stuart M.

    2008-01-01

    Secondary hyperparathyroidism develops relatively early in chronic kidney disease as a consequence of impaired phosphate, calcium, and vitamin D homeostasis. The disease state in chronic kidney disease, which includes the histologic features of bone disease, defined as renal osteodystrophy, and the hormonal and biochemical disturbances, have recently been redefined as a disease syndrome and is referred to as “chronic kidney disease–mineral and bone disorder.” As chronic kidney disease progresses, specific histologic disturbances in the bone develop, which may or may not be predictable from the biochemical and hormonal changes that are associated with chronic kidney disease. In addition, patients may have had underlying bone disease before developing kidney failure or may have been treated with agents that will alter the classical pathologic findings of the bones in chronic kidney disease and their relation to parathyroid hormone. Thus, in stage 5 chronic kidney disease, bone biopsy with quantitative histomorphometric analysis is considered the gold standard in the diagnosis of renal osteodystrophy. In contrast to stage 5 chronic kidney disease, there are very few data on the histologic changes in bone in earlier stages of chronic kidney disease. There also is no adequate information on the etiopathogenesis of bone disease in stages 3 and 4 chronic kidney disease. Thus, because biochemical data cannot predict bone pathology in stages 3 and 4 chronic kidney disease, bone biopsy should be used to define these bone changes and to allow appropriate therapeutic approaches. PMID:18988703

  6. Bone Disease in Multiple Myeloma: Pathophysiology and Management

    PubMed Central

    Hameed, Abdul; Brady, Jennifer J; Dowling, Paul; Clynes, Martin; O’Gorman, Peter

    2014-01-01

    Myeloma bone disease (MBD) is a devastating complication of multiple myeloma (MM). More than 80% of MM patients suffer from destructive bony lesions, leading to pain, fractures, mobility issues, and neurological deficits. MBD is not only a main cause of disability and morbidity in MM patients but also increases the cost of management. Bone destruction and lack of bone formation are main factors in the development of MBD. Some novel factors are found to be involved in the pathogenesis of MBD, eg, receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG) system (RANKL/OPG), Wingless (Wnt), dickkopf-1 (Wnt/DKK1) pathway. The addition of novel agents in the treatment of MM, use of bisphosphonates and other supportive modalities such as radiotherapy, vertebroplasty/kyphoplasty, and surgical interventions, all have significant roles in the treatment of MBD. This review provides an overview on the pathophysiology and management of MBD. PMID:25187738

  7. Magnetic resonance imaging of bone marrow disease in children

    SciTech Connect

    Cohen, M.D.; Klatte, E.C.; Baehner, R.; Smith, J.A.; Martin-Simmerman, P.; Carr, B.E.; Provisor, A.J.; Weetman, R.M.; Coates, T.; Siddiqui, A.

    1984-06-01

    Seven children underwent magnetic resonance imaging (MRI) of the bone marrow: results showed that it is technically feasible to obtain good MR images of marrow in children. MR has detected abnormality in the bone marrow of a child who had metastatic neuroblastoma. The extent of abnormality in the femur correlated well with findings of a bone marrow isotope scan. In one child who had idiopathic aplastic anemia, diseased marrow could not be distinguished from normal marrow on MR images. MRI identified abnormality of the marrow in osteogenic sarcoma, and demonstrated change in response to chemotherapy. It displayed marrow spread of tumors as well as CT. MRI showed marrow abnormality in four children who had leukemia.

  8. Effect of Paget's disease of bone (osteitis deformans) on the progression of prostate cancer bone metastasis

    PubMed Central

    Tu, S-M; Som, A; Tu, B; Logothetis, C J; Lee, M-H; Yeung, S-CJ

    2012-01-01

    Background: Patients with prostate cancer tend to die from bone metastases. Until now, no evidence has shown that Paget's disease of bone (PDB) affects the progression of bone metastasis or overall survival of patients with prostate cancer. Methods: We searched our patient database for men who had presented with prostate cancer and PDB between June 1993 and March 2009, and identified best-matched control patients according to stage, grade, age, date of diagnosis, treatment, and race. Results: Among 1346 consecutive patients with prostate cancer diagnosed before 2008, 15 were confirmed to have comorbid PDB. Twenty-six more were identified from the institutional billing search. Including the 41 best-matched controls, our total study population was 82 patients. In the Kaplan–Meier analysis, we estimated median times from diagnosis of prostate cancer to bone metastasis to be 21.5 years for those with PDB and 9.4 years for those without PDB (P=0.044). Median overall survival times were 11.8 and 9.2 years for the two groups, respectively (P=0.008). Conclusion: For the first time, we have obtained evidence that patients with prostate cancer and PDB have delayed time to bone metastases and improved overall survival than do patients with prostate cancer alone. PMID:22805323

  9. 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

  10. Bone Disease in Newly Diagnosed Lupus Nephritis Patients

    PubMed Central

    Resende, Aline Lázara; dos Reis, Luciene Machado; Dias, Cristiane Bitencourt; Custódio, Melani Ribeiro; Jorgetti, Vanda; Woronik, Viktoria

    2014-01-01

    Introduction Bone loss in Lupus Nephritis (LN) patients is common and multifactorial. The aim of this study was to evaluate the bone status of newly diagnosed LN patients and their correlation with inflammatory factors involved in LN physiopathology. Methods We studied 15 pre-menopausal patients with ≤2 months of diagnosed SLE and LN. Patients with prior kidney or bone disease were excluded. In addition to biochemical evaluation (including 25-hydroxyvitamin D3 [25(OH)D] and Monocyte Chemotactic Protein (MCP1) dosage), we performed bone biopsies followed by osteoblast culture, histomorphometric and immunohistochemistry analysis. Results LN patients presented a mean age of 29.5±10 years, a proteinuria of 4.7±2.9 g/day and an estimated glomerular filtration rate (GFR) of 37(31–87) ml/min/1,73 m2. They were on glucocorticoid therapy for 34±12 days. All patients presented vitamin D insufficiency (9.9±4.4 ng/ml, range 4–20). Urinary MCP1 correlated negatively with 25(OH)D (r = −0.53, p = 0.003) and positively with serum deoxypyridinoline (r = 0.53, p = 0.004). Osteoblasts isolated from LN bone biopsies presented a significantly higher expression of MCP-1 when compared to controls (32.0.±9.1 vs. 22.9±5.3 mean fluorescence intensities, p = 0.01). LN patients presented a significantly reduced osteoid volume, osteoid thickness, osteoid surface, mineralization surface and bone formation rate, associated with an increased eroded surface and osteoclast surface. Patient’s bone specimens demonstrated a reduced immunostaining for osteoprotegerin (0.61±0.82 vs. 1.08±0.50%, p = 0.003), and an increased expression of Receptor Activator of NF-κB ligand (RANKL) (1.76±0.92 vs. 0.41±0.28%, p<0.001) when compared to controls. Discussion Newly diagnosed LN patients presented a significant disturbance in bone metabolism, characterized by an impaired bone formation and mineralization, associated with an increase in resorption parameters

  11. Bones of contention: bone mineral density recovery in celiac disease--a systematic review.

    PubMed

    Grace-Farfaglia, Patricia

    2015-05-07

    Metabolic bone disease is a frequent co-morbidity in newly diagnosed adults with celiac disease (CD), an autoimmune disorder triggered by the ingestion of dietary gluten. This systematic review of studies looked at the efficacy of the gluten-free diet, physical activity, nutrient supplementation, and bisphosphonates for low bone density treatment. Case control and cohort designs were identified from PubMed and other academic databases (from 1996 to 2015) that observed newly diagnosed adults with CD for at least one year after diet treatment using the dual-energy x-ray absorptiometry (DXA) scan. Only 20 out of 207 studies met the inclusion criteria. Methodological quality was assessed using the Strengthening of the Reporting of Observational Studies in Epidemiology (STROBE) statement checklist. Gluten-free diet adherence resulted in partial recovery of bone density by one year in all studies, and full recovery by the fifth year. No treatment differences were observed between the gluten-free diet alone and diet plus bisphosphonates in one study. For malnourished patients, supplementation with vitamin D and calcium resulted in significant improvement. Evidence for the impact of physical activity on bone density was limited. Therapeutic strategies aimed at modifying lifestyle factors throughout the lifespan should be studied.

  12. Bone disease in multiple myeloma and precursor disease: novel diagnostic approaches and implications on clinical management.

    PubMed

    Kristinsson, Sigurdur Y; Minter, Alex R; Korde, Neha; Tan, Esther; Landgren, Ola

    2011-07-01

    The manifestations of bone involvement in patients with multiple myeloma (MM) can have devastating clinical effects and increase mortality. Recent studies demonstrate that patients with the precursor conditions smoldering MM (SMM) and monoclonal gammopathy of undetermined significance (MGUS) show evidence of bone disease and increased risk of fractures. The understanding of the pathogenesis of bone disease in MM has expanded in recent years. The traditional skeletal survey will probably be replaced by newer and more sensitive imaging techniques, which may have a prognostic impact and change our definition of MGUS and SMM. Bisphosphonates are recommended to prevent skeletal events in patients with MM, and have also been studied in SMM and MGUS. This article summarizes the current knowledge of bone disease in plasma cell disorders, and discusses the current standard and future role of novel imaging techniques, as well as the evidence and current guidelines for bisphosphonates in MM, SMM and MGUS.

  13. Bone sarcomas in Paget disease: a study of 85 patients

    SciTech Connect

    Smith, J.; Botet, J.F.; Yeh, S.D.J.

    1984-09-01

    This is a comprehensive review of 85 patients who had bone sarcoma associated with Paget disease and who were seen at Memorial Sloan-Kettering Cancer Center between 1927 and 1982. There was an almost equal distribution of tumors in the axial and the appendicular skeletons. The pelvis, humerus, femur, and skull were the tumor sites in 80% of cases. The tumors were bulky large soft tissue masses. Lytic lesions were more common than sclerotic lesions. Methylene diphosphonate scans of the bone often showed a cold area that was associated with marked increase in uptake on the gallium scan. Angiography, which was performed in 13 patients, was useful, but CT was much more helpful in showing the soft tissue mass as well as the extent of bony disease. Only three patients in this study survived for five years.

  14. [Paget's disease mimicking metastatic prostate cancer on bone scan image : a case report].

    PubMed

    Fukushi, Ken; Koie, Takuya; Yamamoto, Hayato; Okamoto, Akiko; Imai, Atsushi; Hatakeyama, Shingo; Yoneyama, Takahiro; Hashimoto, Yasuhiro; Ohyama, Chikara

    2013-04-01

    A 61-year-old man was referred to our hospital complaining of elevated serum prostate-specific antigen (PSA) (5.1 ng/ml). Histopathologic diagnosis with trans-rectal prostate biopsy specimen was adenocarcinoma, Gleason score 4+5 = 9. Bone scintigraphy revealed an abnormal uptake on left coxal bone. The patient was diagnosed with prostate cancer with bone metastasis. He received androgen deprivation therapy for two years. Serum PSA decreased to an undetected level. However, the abnormal activity of left coxal bone lesion was not changed on bone scintigraphy. Coxal bone biopsy was performed. The bone lesion was histopathologically diagnosed as Paget's disease of bone.

  15. Understanding the Delay in Onset of Pagets Disease of Bone

    DTIC Science & Technology

    2015-09-01

    has passed, is unclear. Understanding the genetics underlying this disease process and how the predisposing mutation interacts with the measles virus...suppressing gene expression in the cell. Then, over the years, a chance genetic event in a single bone cell containing the measles virus results in the...we were able to generate a genetic signature from this comparison of genes that were turned on or turned off in the presence of the measles’ genome

  16. Brittle diabetes: Psychopathology and personality.

    PubMed

    Pelizza, Lorenzo; Pupo, Simona

    The term "brittle" is used to describe an uncommon subgroup of patients with type I diabetes whose lives are disrupted by severe glycaemic instability with repeated and prolonged hospitalization. Psychosocial problems are the major perceived underlying causes of brittle diabetes. Aim of this study is a systematic psychopathological and personological assessment of patients with brittle diabetes in comparison with subjects without brittle diabetes, using specific parameters of general psychopathology and personality disorders following the multi-axial format of the current DSM-IV-TR (Diagnostic and Statistical manual of Mental Disorders - IV Edition - Text Revised) diagnostic criteria for mental disorders. Patients comprised 42 subjects with brittle diabetes and a case-control group of 42 subjects with stable diabetes, matched for age, gender, years of education, and diabetes duration. General psychopathology and the DSM-IV-TR personality disorders were assessed using the Symptom Checklist-90-Revised (SCL-90-R) and the Structured Clinical Interview for axis II personality Disorders (SCID-II). The comparison for SCL-90-R parameters revealed no differences in all primary symptom dimensions and in the three global distress indices between the two groups. However, patients with brittle diabetes showed higher percentages in borderline, histrionic, and narcissistic personality disorder. In this study, patients with brittle diabetes show no differences in terms of global severity of psychopathological distress and specific symptoms of axis I DSM-IV-TR psychiatric diagnoses in comparison with subjects without brittle diabetes. Differently, individuals with brittle diabetes are more frequently affected by specific DSM-IV-TR cluster B personality disorders.

  17. Denosumab: the era of targeted therapies in bone metastatic diseases.

    PubMed

    Santini, D; Fratto, M E; Vincenzi, B; Napoli, N; Galluzzo, S; Tantardini, M; Abbruzzese, A; Caraglia, M; Tonini, G

    2009-11-01

    This system constituted of the Receptor Activator of nuclear Factor-kB Ligand (RANKL), the Receptor Activator of Nuclear Factor-kB (RANK) and by the decoy Receptor Osteoprotegerin (OPG) plays a central role in bone resorption. Denosumab (AMG 162) is an investigational fully human monoclonal antibody with a high affinity and specificity for RANKL.This review will critically describe and discuss the recent results of clinical trial investigating denosumab in different settings of medical oncology. In particular, we will report the recently published data of clinical trials investigating denosumab in prevention of cancer treatment induced bone loss (CTIBL), in prevention of skeletal related events (SREs) in bone metastatic patients and the ongoing studies in prevention of disease recurrence in the adjuvant setting of solid tumours. The clinical data that will be reported in this review represent the first step in a path that will conduct us to explore new horizons in the field of bone health care in cancer patients.

  18. The Kidney-Vascular-Bone Axis in the Chronic Kidney Disease-Mineral Bone Disorder

    PubMed Central

    Seifert, Michael E.; Hruska, Keith A.

    2015-01-01

    The last 25 years have been characterized by dramatic improvements in short-term patient and allograft survival after kidney transplantation. Long-term patient and allograft survival remains limited by cardiovascular disease and chronic allograft injury, among other factors. Cardiovascular disease remains a significant contributor to mortality in native chronic kidney disease as well, as cardiovascular mortality in chronic kidney disease more than doubles that of the general population. The chronic kidney disease-mineral bone disorder (CKD-MBD) is a syndrome recently coined to embody the biochemical, skeletal, and cardiovascular pathophysiology that results from disrupting the complex systems biology between the kidney, skeleton, and cardiovascular system in native and transplant kidney disease. The CKD-MBD is a unique kidney disease-specific syndrome containing novel cardiovascular risk factors, with an impact reaching far beyond traditional notions of renal osteodystrophy and hyperparathyroidism. This Overview reviews current knowledge of the pathophysiology of the CKD-MBD, including emerging concepts surrounding the importance of circulating pathogenic factors released from the injured kidney that directly cause cardiovascular disease in native and transplant chronic kidney disease, with potential application to mechanisms of chronic allograft injury and vasculopathy. PMID:26356179

  19. The Kidney-Vascular-Bone Axis in the Chronic Kidney Disease-Mineral Bone Disorder.

    PubMed

    Seifert, Michael E; Hruska, Keith A

    2016-03-01

    The last 25 years have been characterized by dramatic improvements in short-term patient and allograft survival after kidney transplantation. Long-term patient and allograft survival remains limited by cardiovascular disease and chronic allograft injury, among other factors. Cardiovascular disease remains a significant contributor to mortality in native chronic kidney disease as well as cardiovascular mortality in chronic kidney disease more than doubles that of the general population. The chronic kidney disease (CKD)-mineral bone disorder (MBD) is a syndrome recently coined to embody the biochemical, skeletal, and cardiovascular pathophysiology that results from disrupting the complex systems biology between the kidney, skeleton, and cardiovascular system in native and transplant kidney disease. The CKD-MBD is a unique kidney disease-specific syndrome containing novel cardiovascular risk factors, with an impact reaching far beyond traditional notions of renal osteodystrophy and hyperparathyroidism. This overview reviews current knowledge of the pathophysiology of the CKD-MBD, including emerging concepts surrounding the importance of circulating pathogenic factors released from the injured kidney that directly cause cardiovascular disease in native and transplant chronic kidney disease, with potential application to mechanisms of chronic allograft injury and vasculopathy.

  20. National Institutes of Health Osteoporosis and Related Bone Diseases~National Resource Center

    MedlinePlus

    ... Language Publications (en español) | Asian-Language Publications NIH Osteoporosis and Related Bone Diseases ~ NIH National Resource Center ... Font Size | S S M M L L Bone Basics Osteoporosis Osteogenesis Imperfecta Paget’s Disease of Bone Related Topics ...

  1. Wolman disease successfully treated by bone marrow transplantation.

    PubMed

    Krivit, W; Peters, C; Dusenbery, K; Ben-Yoseph, Y; Ramsay, N K; Wagner, J E; Anderson, R

    2000-09-01

    Wolman disease is characterized by severe diarrhea and malnutrition leading to death during infancy. Lysosomal acid lipase deficiency is the cause of the symptoms and signs. It is inherited in an autosomal recessive manner. All Wolman disease patients have adrenal gland calcification. Previous therapeutic attempts have failed to provide remission. We report successful long-term bone marrow engraftment in a patient with Wolman disease resulting in continued normalization of peripheral leukocyte lysosomal acid lipase enzyme activity. Diarrhea is no longer present. Now, at 4 years of age, this patient is gaining developmental milestones. Cholesterol and triglyceride levels are normal. Liver function is normal. This is the first long-term continued remission reported for Wolman disease.

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

    PubMed

    Johnson, Mark L

    2016-01-01

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

  3. Recommendations for evaluation and management of bone disease in HIV.

    PubMed

    Brown, Todd T; Hoy, Jennifer; Borderi, Marco; Guaraldi, Giovanni; Renjifo, Boris; Vescini, Fabio; Yin, Michael T; Powderly, William G

    2015-04-15

    Thirty-four human immunodeficiency virus (HIV) specialists from 16 countries contributed to this project, whose primary aim was to provide guidance on the screening, diagnosis, and monitoring of bone disease in HIV-infected patients. Four clinically important questions in bone disease management were identified, and recommendations, based on literature review and expert opinion, were agreed upon. Risk of fragility fracture should be assessed primarily using the Fracture Risk Assessment Tool (FRAX), without dual-energy X-ray absorptiometry (DXA), in all HIV-infected men aged 40-49 years and HIV-infected premenopausal women aged ≥40 years. DXA should be performed in men aged ≥50 years, postmenopausal women, patients with a history of fragility fracture, patients receiving chronic glucocorticoid treatment, and patients at high risk of falls. In resource-limited settings, FRAX without bone mineral density can be substituted for DXA. Guidelines for antiretroviral therapy should be followed; adjustment should avoid tenofovir disoproxil fumarate or boosted protease inhibitors in at-risk patients. Dietary and lifestyle management strategies for high-risk patients should be employed and antiosteoporosis treatment initiated.

  4. A new tablet brittleness index.

    PubMed

    Gong, Xingchu; Sun, Changquan Calvin

    2015-06-01

    Brittleness is one of the important material properties that influences the success or failure of powder compaction. We have discovered that the reciprocal of diametrical elastic strain at fracture is the most suitable tablet brittleness indices (TBIs) for quantifying brittleness of pharmaceutical tablets. The new strain based TBI is supported by both theoretical considerations and a systematic statistical analysis of friability data. It is sufficiently sensitive to changes in both tablet compositions and compaction parameters. For all tested materials, it correctly shows that tablet brittleness increases with increasing tablet porosity for the same powder. In addition, TBI increases with increasing content of a brittle excipient, lactose monohydrate, in the mixtures with a plastic excipient, microcrystalline cellulose. A probability map for achieving less than 1% tablet friability at various combinations of tablet tensile strength and TBI was constructed. Data from marketed tablets validate this probability map and a TBI value of 150 is recommended as the upper limit for pharmaceutical tablets. This TBI can be calculated from the data routinely obtained during tablet diametrical breaking test, which is commonly performed for assessing tablet mechanical strength. Therefore, it is ready for adoption for quantifying tablet brittleness to guide tablet formulation development since it does not require additional experimental work.

  5. The "bone morphogenic proteins" pathways in bone and joint diseases: translational perspectives from physiopathology to therapeutic targets.

    PubMed

    Biver, Emmanuel; Hardouin, Pierre; Caverzasio, Joseph

    2013-02-01

    A large body of evidence supports an important role of bone morphogenic proteins (BMPs) pathways in skeletal development in the embryo. BMPs are also involved in skeletal homeostasis and diseases in the adult. They were first identified as major bone anabolic agents and recent advances indicate that they also regulate osteoclastogenesis and joint components via multiple cross-talks with other signaling pathways. This review attempts to integrate these data in the pathogenesis of bone and joints diseases, such as osteoporosis, fracture healing, osteoarthritis, inflammatory arthritis, or bone metastasis. The use of recombinant BMPs in bone tissue engineering and in the treatment of skeletal diseases, or future therapeutic strategies targeting BMPs signal and its regulators, will be discussed based on these considerations.

  6. Molecular disease map of bone characterizing the postmenopausal osteoporosis phenotype.

    PubMed

    Jemtland, Rune; Holden, Marit; Reppe, Sjur; Olstad, Ole K; Reinholt, Finn P; Gautvik, Vigdis T; Refvem, Hilde; Frigessi, Arnoldo; Houston, Brian; Gautvik, Kaare M

    2011-08-01

    Genome-wide gene expressions in bone biopsies from patients with postmenopausal osteoporosis and healthy controls were profiled, to identify osteoporosis candidate genes. All osteoporotic patients (n = 27) in an unbiased cohort of Norwegian women presented with bone mineral density (BMD) T-scores of less than -2.5 SD and one or more confirmed low-energy fracture(s). A validation group (n = 18) had clinical and laboratory parameters intermediate to the control (n = 39) and osteoporosis groups. RNA from iliac crest bone biopsies were analyzed by Affymetrix microarrays and real-time reverse-transcriptase polymerase chain reaction (RT-PCR). Differentially expressed genes in osteoporosis versus control groups were identified using the Bayesian ANOVA for microarrays (BAMarray) method, whereas the R-package Limma (Linear Models for Microarray Data) was used to determine whether these transcripts were explained by disease, age, body mass index (BMI), or combinations thereof. Laboratory tests showed normal ranges for the cohort. A total of 609 transcripts were differentially expressed in osteoporotic patients relative to controls; 256 transcripts were confirmed for disease when controlling for age or BMI. Most of the osteoporosis susceptibility genes (80%) also were confirmed to be regulated in the same direction in the validation group. Furthermore, 217 of 256 transcripts were correlated with BMD (adjusted for age and BMI) at various skeletal sites (|r| > 0.2, p < .05). Among the most distinctly expressed genes were Wnt antagonists DKK1 and SOST, the transcription factor SOX4, and the bone matrix proteins MMP13 and MEPE, all reduced in osteoporosis versus control groups. Our results identify potential osteoporosis susceptibility candidate genes adjusted for confounding factors (ie, age and BMI) with or without a significant correlation with BMD.

  7. [New Developments in CKD-MBD. Bone quality and fracture in patients with chronic kidney disease].

    PubMed

    Iwasaki, Yoshiko; Yamato, Hideyuki

    2014-12-01

    Chronic kidney disease (CKD) patients have an extremely increased risk of fragility fractures, but the underling pathophysiological mechanisms remain obscure. Recently, the progresses of analysis technology have revealed the changes of bone quality in CKD condition. In particular, we can observe the characteristic changes of bone microarchitecture and bone chemical compositions in both human bone biopsy samples and experimental animal bones. Here, I will provide a short review on these bone quality factors and discuss on the relationship between bone quality and fracture in CKD patients.

  8. Marathon of eponyms: 16 Paget disease of bone.

    PubMed

    Scully, C; Langdon, J; Evans, J

    2011-03-01

    The use of eponyms has long been contentious, but many remain in common use, as discussed elsewhere (Editorial: Oral Diseases. 2009: 15; 185). The use of eponyms in diseases of the head and neck is found mainly in specialties dealing with medically compromised individuals (paediatric dentistry, special care dentistry, oral and maxillofacial medicine, oral and maxillofacial pathology, oral and maxillofacial radiology and oral and maxillofacial surgery) and particularly by hospital-centred practitioners. This series has selected some of the more recognised relevant eponymous conditions and presents them alphabetically. The information is based largely on data available from MEDLINE and a number of internet websites as noted below: the authors would welcome any corrections. This document summarises data about Paget disease of bone.

  9. Circulating microRNAs as novel biomarkers for bone diseases - Complex signatures for multifactorial diseases?

    PubMed

    Hackl, Matthias; Heilmeier, Ursula; Weilner, Sylvia; Grillari, Johannes

    2016-09-05

    Biomarkers are essential tools in clinical research and practice. Useful biomarkers must combine good measurability, validated association with biological processes or outcomes, and should support clinical decision making if used in clinical practice. Several types of validated biomarkers have been reported in the context of bone diseases. However, because these biomarkers face certain limitations there is an interest in the identification of novel biomarkers for bone diseases, specifically in those that are tightly linked to the disease pathology leading to increased fracture-risk. MicroRNAs (miRNAs) are the most abundant RNA species to be found in cell-free blood. Encapsulated within microvesicles or bound to proteins, circulating miRNAs are remarkably stable analytes that can be measured using gold-standard technologies such as quantitative polymerase-chain-reaction (qPCR). Nevertheless, the analysis of circulating miRNAs faces several pre-analytical as well as analytical challenges. From a biological view, there is accumulating evidence that miRNAs play essential roles in the regulation of various biological processes including bone homeostasis. Moreover, specific changes in miRNA transcription levels or miRNA secretory levels have been linked to the development and progression of certain bone diseases. Only recently, results from circulating miRNAs analysis in patients with osteopenia, osteoporosis and fragility fractures have been reported. By comparing these findings to studies on circulating miRNAs in cellular senescence and aging or muscle physiology and sarcopenia, several overlaps were observed. This suggests that signatures observed during osteoporosis might not be specific to the pathophysiology in bone, but rather integrate information from several tissue types. Despite these promising first data, more work remains to be done until circulating miRNAs can serve as established and robust diagnostic tools for bone diseases in clinical research, clinical

  10. Metastatic Bone Disease: Role of Transcription Factors and Future Targets

    PubMed Central

    Pratap, Jitesh; Lian, Jane B.; Stein, Gary S.

    2010-01-01

    Progression of cancer from the earliest event of cell transformation through stages of tumor growth and metastasis at a distal site involves many complex biological processes. Underlying the numerous responses of cancer cells to the tumor microenvironment which support their survival, migration and metastasis are transcription factors that regulate the expression of genes reflecting properties of the tumor cell. A number of transcription factors have been identified that play key roles in promoting oncogenesis, tumor growth, metastasis and tissue destruction. Relevant to solid tumors and leukemias, tissue specific transcription factors that are deregulated resulting from mutations, being silenced or aberrantly expressed, have been well characterized. These are the master transcription factors of the Runx family of genes, the focus of this review, with emphasis placed on Runx2 that is abnormally expressed at very high levels in cancer cell lines that are metastatic to bone. Recent evidence has identified a correlation of Runx2 levels in advanced stages of prostate and breast cancer and demonstrated that effective depletion of Runx2 by RNA interference inhibits migration and invasive properties of the cells prevents metastatic bone disease. This striking effect is consistent with the broad spectrum of Runx2 properties in activating many genes in tumor cells that have already been established as indicators of bone metastasis in poor prognosis. Potential strategies to translate these findings for therapeutic applications are discussed. PMID:20561908

  11. Bone Marrow Stem Cell Contribution to Pulmonary Homeostasis and Disease

    PubMed Central

    McDonald, Lindsay T; LaRue, Amanda C

    2015-01-01

    The understanding of bone marrow stem cell plasticity and contribution of bone marrow stem cells to pathophysiology is evolving with the advent of innovative technologies. Recent data has led to new mechanistic insights in the field of mesenchymal stem cell (MSC) research, and an increased appreciation for the plasticity of the hematopoietic stem cell (HSC). In this review, we discuss current research examining the origin of pulmonary cell types from endogenous lung stem and progenitor cells as well as bone marrow-derived stem cells (MSCs and HSCs) and their contributions to lung homeostasis and pathology. We specifically highlight recent findings from our laboratory that demonstrate an HSC origin for pulmonary fibroblasts based on transplantation of a clonal population of cells derived from a single HSC. These findings demonstrate the importance of developing an understanding of the sources of effector cells in disease state. Finally, a perspective is given on the potential clinical implications of these studies and others addressing stem cell contributions to lung tissue homeostasis and pathology. PMID:26798846

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

    MedlinePlus

    ... Disease of Bone Paget’s Disease Basics Facts a New Patient Needs to Know About Paget’s Disease of ... geographical areas, including England, the United States, Australia, New Zealand, and Western Europe. It is not common ...

  13. Bone imaging and fracture risk assessment in kidney disease.

    PubMed

    Jamal, Sophie A; Nickolas, Thomas L

    2015-06-01

    Fractures are more common and are associated with greater morbidity and morality in patients with kidney disease than in members of the general population. Thus, it is troubling that in chronic kidney disease (CKD) patients there has been a paradoxical increase in fracture rates over the past 20 years compared to the general population. Increased fracture incidence in CKD patients may be driven in part by the lack of screening for fracture risk. In the general population, dual energy X-ray absorptiometry (DXA) is the clinical standard to stratify fracture risk, and its use has contributed to decreases in fracture incidence. In contrast, in CKD, fracture risk screening with DXA has been uncommon due to its unclear efficacy in predicting fracture and its inability to predict type of renal osteodystrophy. Recently, several prospective studies conducted in patients across the spectrum of kidney disease have demonstrated that bone mineral density measured by DXA predicts future fracture risk and that clinically relevant information regarding fracture risk is provided by application of the World Health Organization cutoffs for osteopenia and osteoporosis to DXA measures. Furthermore, novel high-resolution imaging tools, such as high-resolution peripheral quantitative computed tomography (HR-pQCT), have been used to elucidate the effects of kidney disease on cortical and trabecular microarchitecture and bone strength and to identify potential targets for strategies that protect against fractures. This review will discuss the updated epidemiology of fractures in CKD, fracture risk screening by DXA, and the utility of state-of-the art imaging methods to uncover the effects of kidney disease on the skeleton.

  14. Risk factors for developing mineral bone disease in phenylketonuric patients.

    PubMed

    Mirás, Alicia; Bóveda, M Dolores; Leis, María R; Mera, Antonio; Aldámiz-Echevarría, Luís; Fernández-Lorenzo, José R; Fraga, José M; Couce, María L

    2013-03-01

    There is a compromised bone mass in phenylketonuria patients compared with normal population, but the mechanisms responsible are still a matter of investigation. In addition, tetrahydrobiopterin therapy is a new option for a significant proportion of these patients and the prevalence of mineral bone disease (MBD) in these patients is unknown. We conducted a cross-sectional observational study including 43 phenylketonuric patients. Bone densitometry, nutritional assessment, physical activity questionnaire, biochemical parameters, and molecular study were performed in all patients. Patients were stratified by phenotype, age and type of treatment. The MBD prevalence in phenylketonuria was 14%. Osteopenic and osteoporotic (n=6 patients) had an average daily natural protein intake significantly lower than the remaining (n=37) patients with PKU (14.33 ± 8.95 g vs 21.25 ± 20.85 g). Besides, a lower body mass index was found. There were no statistical differences in physical activity level, calcium, phosphorus and fat intake, and in phenylalanine, vitamin D, paratohormone, docosahexaenoic and eicosapentaenoic acid blood levels. Mutational spectrum was found in up to 30 different PAH genotypes and no relationship was established among genotype and development of MBD. None of the twelve phenylketonuric patients treated with tetrahydrobiopterin (27.9%), for an average of 7.1 years, developed MBD. Natural protein intake and blood levels of eicosapentaenoic acid were significantly higher while calcium intake was lower in these patients. This study shows that the decrease in natural protein intake can play an important role in MBD development in phenylketonuric patients. Therapy with tetrahydrobiopterin allows a more relaxed protein diet, which is associated with better bone mass.

  15. The Rare Bone Disease Working Group: report from the 2016 American Society for Bone and Mineral Research Annual Meeting.

    PubMed

    Drake, Matthew T; Collins, Michael T; Hsiao, Edward C

    2017-01-20

    A working group on rare bone diseases was held in Atlanta, Georgia as part of the 2016 annual meeting of the American Society for Bone and Mineral Research. The meeting was organized by Matthew Drake. Given recent advances in our understanding of fibrodysplasia ossificans progressiva (FOP), the initial portion of the program was devoted to basic, translational, and clinical aspects of FOP. The remainder of the program was divided into updates on an array of rare bone diseases as detailed below. In total, there were more than 120 scientists from academia and industry in attendance.

  16. Computer-assisted quantitative evaluation of bisphosphonate treatment for Paget's disease of bone using the bone scan index

    PubMed Central

    Nagano, Satoshi; Nakamura, Shunsuke; Shimada, Hirofumi; Yokouchi, Masahiro; Setoguchi, Takao; Ishidou, Yasuhiro; Sasaki, Hiromi; Komiya, Setsuro

    2016-01-01

    The purpose of the present study was to analyze the effect of treatment of Paget's disease of bone (PDB) with bone scintigraphy using a computer-assisted diagnosis system (BONENAVI) that quantitatively evaluates bone metabolism. Seven patients with PDB (three male, four female; average age, 60 years; age range, 33–80 years) underwent bone scintigraphy and measurement of serum alkaline phosphatase (ALP), bone-specific ALP (BAP), serum cross-linked N-telopeptide (NTx) of type I collagen, urinary NTx, and deoxypyridinoline (DPD) before and after bisphosphonate treatment. Bone scan index (BSI), artificial neural network (ANN) value, and hotspot number (HSn) were calculated using BONENAVI software. Mean follow-up period was 22 months (range, 11–35 months). Among three BONENAVI parameters (ANN, BSI, and HSn), only BSI was significantly lower after bisphosphonate treatment as compared with before. All bone metabolic markers excluding DPD were significantly lower following bisphosphonate treatment than before. Bone formation markers (ALP and BAP) were significantly lower than bone resorption markers (U-NTx and S-NTx). The correlation of BONENAVI parameters with four bone metabolic markers was analyzed before and after bisphosphonate treatment. Before treatment, the majority of the four markers did not correlate with the BONENAVI parameters. In contrast, post-treatment ALP, BAP, and U-NTx were significantly correlated with BSI and HSn. To the best of our knowledge, this is the first study to evaluate the treatment of PDB by bone scintigraphy using a computer-assisted diagnosis system that quantitatively evaluates bone metabolism. The findings demonstrated that, using BONENAVI software, bone scintigraphy is able to quantitatively and spatially evaluate the bisphosphonate treatment effect, particularly in patients with polyostotic PDB. PMID:28105116

  17. Dynamic failure in brittle solids

    SciTech Connect

    Grady, D.E.

    1994-04-01

    Failure of brittle solids within the extremes of the shock loading environment is not well understood. Recent shock-wave data on compression shear failure and tensile spall failure for selected high-strength ceramics are presented and used to examine the mechanisms of dynamic failure. Energy-based theories are used to bound the measured strength properties. A new concept of failure waves in brittle solids is explored in light of the kinetic processes of high-rate fracture. Classical failure criteria are compared with the present base of dynamic strength data on ceramics.

  18. The fracture mechanics of human bone: influence of disease and treatment

    PubMed Central

    Zimmermann, Elizabeth A; Busse, Björn; Ritchie, Robert O

    2015-01-01

    Aging and bone diseases are associated with increased fracture risk. It is therefore pertinent to seek an understanding of the origins of such disease-related deterioration in bone's mechanical properties. The mechanical integrity of bone derives from its hierarchical structure, which in healthy tissue is able to resist complex physiological loading patterns and tolerate damage. Indeed, the mechanisms through which bone derives its mechanical properties make fracture mechanics an ideal framework to study bone's mechanical resistance, where crack-growth resistance curves give a measure of the intrinsic resistance to the initiation of cracks and the extrinsic resistance to the growth of cracks. Recent research on healthy cortical bone has demonstrated how this hierarchical structure can develop intrinsic toughness at the collagen fibril scale mainly through sliding and sacrificial bonding mechanisms that promote plasticity. Furthermore, the bone-matrix structure develops extrinsic toughness at much larger micrometer length-scales, where the structural features are large enough to resist crack growth through crack-tip shielding mechanisms. Although healthy bone tissue can generally resist physiological loading environments, certain conditions such as aging and disease can significantly increase fracture risk. In simple terms, the reduced mechanical integrity originates from alterations to the hierarchical structure. Here, we review how human cortical bone resists fracture in healthy bone and how changes to the bone structure due to aging, osteoporosis, vitamin D deficiency and Paget's disease can affect the mechanical integrity of bone tissue. PMID:26380080

  19. Epidemiology and pathology of Paget's disease of bone - a review.

    PubMed

    Nebot Valenzuela, Elena; Pietschmann, Peter

    2017-02-01

    Paget's disease of bone (PDB) is a noninflammatory, metabolic, skeletal disorder characterized by localized excessive osteoclastic bone resorption that is followed by compensatory increased osteoblastic activity leading to unstructured, fibroblastic, and biomechanically unstable bone. As a result, there is deformity and enlargement of the bone with a defective and disorganized pattern. Here, we review the epidemiology, etiology, pathology, macrostructure, histology, and quantitative histomorphometry findings of PDB. Hyperosteoclastosis and poor definition of the boundary between cortical and medullary bone are the main histological findings in PDB. Additionally, Pagetic bone is also characterized by hypertrophy and alteration of trabecular parameters.

  20. Pathological fracture of the femur in a patient with Paget's disease of bone: a case report.

    PubMed

    Petrescu, Pompiliu HoraŢiu; Izvernariu, Dragoş Andrei; Iancu, Cătălina; Dinu, Gabriel Ovidiu; Berceanu-Văduva, Marcel Mihai; Crişan, Dan; Iacob, Mihaela; Bucur, Venera Margareta; RăuŢia, Ion Călin; Prejbeanu, Ion Radu; Dema, Sorin; DuŢă, Ciprian Constantin

    2016-01-01

    Paget's disease of bone is a benign disease characterized by exaggerated remodeling of the bone matrix after osteoclast-mediated bone destruction. Its etiology is still unknown, despite the fact that it was discovered and described in 1877, but genetic factors and environmental triggers were shown to play their part in the pathogenesis of the disease. The main clinical presentations of the disease are related to bone pain and deformities. Radiological diagnosis is the main detection tool, though many monostotic Paget's disease cases may remain undiagnosed. We present the case of an 81-year-old male patient admitted to the Clinic of Orthopedics, Emergency County Hospital, Timisoara, Romania, with intense pain and deformity of the upper left thigh. Radiological examination performed shows a complete fracture of the upper third diaphysis of the left femur with suggestive signs for Paget's disease of the bone therefore a biopsy was taken and the patient was treated by surgical realignment with favorable evolution. He was discharged 13 days after surgery. The biopsy of the bone revealed extensive bone remodeling with numerous osteoclasts and extensive bone matrix deposition, unevenly stained and unevenly mineralized and reverse cement lines, which are consistent with the diagnosis of Paget's disease of the bone. Histomorphometric analysis show intense matrix deposition with a highly active remodeling process. Computed tomography (CT) scans were performed three years later and show the extension of the disease into the lower half of the left femur.

  1. [Updates on Lifestyle-Related Diseases and Bone Metabolism. Bisphosphonates for lifestyle-related disease].

    PubMed

    Okada, Yosuke; Tanaka, Yoshiya

    2014-11-01

    A lifestyle-related disease and osteoporosis are diseases to increase with aging and a lifestyle-related disease has an influence on the bone metabolism. Because the number of patients with lifestyle-related disease is getting larger, it is necessary to prevent fracture in those. Unfortunately, substantial randomized control studies are yet to be done in patients with lifestyle-related disease to clarify if anti-osteoporotic drugs are effective to prevent fractures. It is suggested by the subanalysis in the existing clinical study with usefulness of bisphosphonates with evidence as an osteoporotic therapeutic drug in life-related disease. Here I will review about the effective and problem with bisphosphonate for the lifestyle-related disease with arteriosclerosis.

  2. Dual Therapeutic Action of a Neutralizing Anti-FGF2 Aptamer in Bone Disease and Bone Cancer Pain

    PubMed Central

    Jin, Ling; Nonaka, Yosuke; Miyakawa, Shin; Fujiwara, Masatoshi; Nakamura, Yoshikazu

    2016-01-01

    Fibroblast growth factor 2 (FGF2) plays a crucial role in bone remodeling and disease progression. However, the potential of FGF2 antagonists for treatment of patients with bone diseases has not yet been explored. Therefore, we generated a novel RNA aptamer, APT-F2, specific for human FGF2 and characterized its properties in vitro and in vivo. APT-F2 blocked binding of FGF2 to each of its four cellular receptors, inhibited FGF2-induced downstream signaling and cells proliferation, and restored osteoblast differentiation blocked by FGF2. APT-F2P, a PEGylated form of APT-F2, effectively blocked the bone disruption in mouse and rat models of arthritis and osteoporosis. Treatment with APT-F2P also exerted a strong analgesic effect, equivalent to morphine, in a mouse model of bone cancer pain. These findings demonstrated dual therapeutic action of APT-F2P in bone diseases and pain, providing a promising approach to the treatment of bone diseases. PMID:27506449

  3. [Treatment of bone disease in chronic kidney disease and in renal transplant recipients under K/DOQI clinical practice guidelines].

    PubMed

    Tokumoto, Tadahiko; Tanabe, Kazunari; Toma, Hiroshi; Akiba, Takashi

    2004-05-01

    The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (K/DOQI) provides evidence based clinical practice guidelines developed for all phases of kidney disease and related complications, from diagnosis to monitoring and management. Bone disease sets in during the early stages of Chronic Kidney Disease (CKD). Bone disease is observed in almost patients with chronic renal failure and after renal transplantation. Hyperparathyroid (high turnover) bone disease in patients with chronic renal failure is found most frequently followed by mixed osteodystrophy, low-turn over bone disease, and osteomalasia. Ninety to one hundred percent of kidney transplant patients have histological evidence of osteodystrophy and osteopenia (reduction of bone mass) following renal transplantation. Furthermore, osteoporosis is also appeared in many renal transplant recipients. After renal transplantation, renal osteodystrophy generally improves but bone mineral density (BMD) often worsens. When renal bone disease is assessed using a combination of biochemical markers, histology and bone densitometry, early intervention and carefully effective therapies might be reduced the morbidity associated with these common problems.

  4. Mechanical alloying of brittle materials

    NASA Astrophysics Data System (ADS)

    Davis, R. M.; McDermott, B.; Koch, C. C.

    1988-12-01

    Mechanical alloying by high energy ball milling has been observed in systems with nominally brittle components. The phases formed by mechanical alloying of brittle components include solid solutions (Si + Ge → SiGe solid solution), intermetallic compounds (Mn + Bi → MnBi), and amorphous alloys (NiZr2 + Ni11Zr9 → amorphous Ni50Zr50). A key feature of possible mechanisms for mechanical alloying of brittle components is the temperature of the powders during milling. Experiments and a computer model of the kinetics of mechanical alloying were carried out in order to esti-mate the temperature effect. Temperature rises in typical powder alloys during milling in a SPEX mill were estimated to be ≤350 K using the kinetic parameters determined from the computer model. The tempering response of fresh martensite in an Fe-1.2 wt pct C alloy during milling was consistent with the maximum results of the computer model, yielding temperatures in the pow-ders of ≤575 K i.e., ΔT ≤ 300 K). Thermal activation was required for mechanical alloying of Si and Ge powder. No alloying occurred when the milling vial was cooled by liquid nitrogen. The pos-sible mechanisms responsible for material transfer during mechanical alloying of brittle components are considered.

  5. Soft matter: Brittle for breakfast

    NASA Astrophysics Data System (ADS)

    Vandewalle, Nicolas

    2015-10-01

    Crushing a brittle porous medium such as a box of cereal causes the grains to break up and rearrange themselves. A lattice spring model based on simple physical assumptions gives rise to behaviours that are complex enough to reproduce diverse compaction patterns.

  6. Paget's Disease of Bone: A Review of Epidemiology, Pathophysiology and Management

    PubMed Central

    Shaker, Joseph L.

    2009-01-01

    Paget's disease of bone is a common disorder which may affect one or many bones. Although many patients are asymptomatic, a variety of symptoms and complications may occur. Fortunately, effective pharmacologic therapy, primarily with potent bisphosphonates, is now available to treat patients with complications or symptoms. This review of Paget's disease of bone will include epidemiology and pathophysiology, complications and clinical findings, indications for treatment, and the drugs currently available to treat this condition. PMID:22870432

  7. Proceedings of the 2016 Santa Fe Bone Symposium: New Concepts in the Management of Osteoporosis and Metabolic Bone Diseases.

    PubMed

    Lewiecki, E Michael; Bilezikian, John P; Bukata, Susan V; Camacho, Pauline; Clarke, Bart L; McClung, Michael R; Miller, Paul D; Shepherd, John

    2017-02-06

    The Santa Fe Bone Symposium is an annual meeting of healthcare professionals and clinical researchers that details the clinical relevance of advances in knowledge of skeletal diseases. The 17th Santa Fe Bone Symposium was held in Santa Fe, New Mexico, USA, on August 5-6, 2016. The program included plenary lectures, oral presentations by endocrinology fellows, meet-the-professor sessions, and panel discussions, all aimed to provide ample opportunity for interactive discussions among all participants. Symposium topics included recent developments in the translation of basic bone science to patient care, new clinical practice guidelines for postmenopausal osteoporosis, management of patients with disorders of phosphate metabolism, new and emerging treatments for rare bone diseases, strategies to enhance fracture healing, and an update on Bone Health Extension for Community Healthcare Outcomes, using a teleconferencing platform to elevate the level of knowledge of healthcare professionals in underserved communities to deliver best practice care for skeletal diseases. The highlights and important clinical messages of the 2016 Santa Fe Bone Symposium are provided herein by each of the faculty presenters.

  8. Emerging strategies and therapies for treatment of Paget’s disease of bone

    PubMed Central

    Michou, Laëtitia; Brown, Jacques P

    2011-01-01

    Paget’s disease of bone (PDB) is a progressive monostotic or polyostotic metabolic bone disease characterized by focal abnormal bone remodeling, with increased bone resorption and excessive, disorganized, new bone formation. PDB rarely occurs before middle age, and it is the second most frequent metabolic bone disorder after osteoporosis, affecting up to 3% of adults over 55 years of age. One of the most striking and intriguing clinical features is the focal nature of the disorder, in that once the disease is established within a bone, there is only local spread within that bone and no systemic dissemination. Despite many years of intense research, the etiology of PDB has still to be conclusively determined. Based on a detailed review of genetic and viral factors incriminated in PDB, we propose a unifying hypothesis from which we can suggest emerging strategies and therapies. PDB results in weakened bone strength and abnormal bone architecture, leading to pain, deformity or, depending on the bone involved, fracture in the affected bone. The diagnostic assessment includes serum total alkaline phosphatase, total body bone scintigraphy, skull and enlarged view pelvis x-rays, and if needed, additional x-rays. The ideal therapeutic option would eliminate bone pain, normalize serum total alkaline phosphatase with prolonged remission, heal radiographic osteolytic lesions, restore normal lamellar bone, and prevent recurrence and complications. With the development of increasingly potent bisphosphonates, culminating in the introduction of a single intravenous infusion of zoledronic acid 5 mg, these goals of treatment are close to being achieved, together with long-term remission in almost all patients. Based on the recent pathophysiological findings, emerging strategies and therapies are reviewed: ie, pulse treatment with zoledronic acid; denosumab, a fully human monoclonal antibody directed against RANK ligand; tocilizumab, an interleukin-6 receptor inhibitor; odanacatib

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

    PubMed Central

    Rubin, Mishaela R; Patsch, Janina M

    2016-01-01

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

  10. Statistical models of brittle fragmentation

    NASA Astrophysics Data System (ADS)

    Åström, J. A.

    2006-06-01

    Recent developments in statistical models for fragmentation of brittle material are reviewed. The generic objective of these models is understanding the origin of the fragment size distributions (FSDs) that result from fracturing brittle material. Brittle fragmentation can be divided into two categories: (1) Instantaneous fragmentation for which breakup generations are not distinguishable and (2) continuous fragmentation for which generations of chronological fragment breakups can be identified. This categorization becomes obvious in mining industry applications where instantaneous fragmentation refers to blasting of rock and continuous fragmentation to the consequent crushing and grinding of the blasted rock fragments. A model of unstable cracks and crack-branch merging contains both of the FSDs usually related to instantaneous fragmentation: the scale invariant FSD with the power exponent (2-1/D) and the double exponential FSD which relates to Poisson process fragmentation. The FSDs commonly related to continuous fragmentation are: the lognormal FSD originating from uncorrelated breakup and the power-law FSD which can be modeled as a cascade of breakups. Various solutions to the generic rate equation of continuous fragmentation are briefly listed. Simulations of crushing experiments reveal that both cascade and uncorrelated fragmentations are possible, but that also a mechanism of maximizing packing density related to Apollonian packing may be relevant for slow compressive crushing.

  11. Bone mineral density predicts fractures in chronic kidney disease.

    PubMed

    West, Sarah L; Lok, Charmaine E; Langsetmo, Lisa; Cheung, Angela M; Szabo, Eva; Pearce, Dawn; Fusaro, Maria; Wald, Ron; Weinstein, Jordan; Jamal, Sophie A

    2015-05-01

    Fractures are common in chronic kidney disease (CKD). The optimal methods by which to assess fracture risk are unknown, in part, due to a lack of prospective studies. We determined if bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA), and/or high-resolution peripheral quantitative computed tomography (HRpQCT) could predict fractures in men and women ≥18 years old with stages 3 to 5 CKD. BMD was measured by DXA (at the total hip, lumbar spine, ultradistal, and 1/3 radius) and by HRpQCT (at the radius), and subjects were followed for 2 years for incident morphometric spine fractures and low-trauma clinical fractures. The mean age of the subjects was 62 years with equal numbers having stages 3, 4, and 5 CKD. Over 2 years there were 51 fractures in 35 subjects. BMD by DXA at baseline was significantly lower at all sites among those with incident fractures versus those without. For example, the mean BMD at the total hip in those with incident fractures was 0.77 g/cm2 (95% confidence interval [CI], 0.73 to 0.80) and in those without fracture was 0.95 g/cm2 (95% CI, 0.92 to 0.98). Almost all baseline HRpQCT measures were lower in those with incident fracture versus those without. For example, volumetric BMD in those with incident fractures was 232 mg HA/cm3 (95% CI, 213 to 251) and in those without fracture was 317.6 mg HA/cm3 (95% CI, 306 to 329.1). Bone loss occurred in all subjects, but was significantly greater among those with incident fractures. Our data demonstrate that low BMD (by DXA and HRpQCT) and a greater annualized percent decrease in BMD are risk factors for subsequent fracture in men and women with predialysis CKD.

  12. Natural History of Malignant Bone Disease in Gastric Cancer: Final Results of a Multicenter Bone Metastasis Survey

    PubMed Central

    Silvestris, Nicola; Pantano, Francesco; Ibrahim, Toni; Gamucci, Teresa; De Vita, Fernando; Di Palma, Teresa; Pedrazzoli, Paolo; Barni, Sandro; Bernardo, Antonio; Febbraro, Antonio; Satolli, Maria Antonietta; Bertocchi, Paola; Catalano, Vincenzo; Giommoni, Elisa; Comandone, Alessandro; Maiello, Evaristo; Riccardi, Ferdinando; Ferrara, Raimondo; Trogu, Antonio; Berardi, Rossana; Leo, Silvana; Bertolini, Alessandro; Angelini, Francesco; Cinieri, Saverio; Russo, Antonio; Pisconti, Salvatore; Brunetti, Anna Elisabetta; Azzariti, Amalia; Santini, Daniele

    2013-01-01

    Background Bone metastasis represents an increasing clinical problem in advanced gastric cancer (GC) as disease-related survival improves. In literature, few data on the natural history of bone disease in GC are available. Patients and Methods Data on clinicopathology, skeletal outcomes, skeletal-related events (SREs), and bone-directed therapies for 208 deceased GC patients with evidence of bone metastasis were statistically analyzed. Results Median time to bone metastasis was 8 months (CI 95%, 6.125–9.875 months) considering all included patients. Median number of SREs/patient was one. Less than half of the patients (31%) experienced at least one and only 4 and 2% experienced at least two and three events, respectively. Median times to first and second SRE were 2 and 4 months, respectively. Median survival was 6 months after bone metastasis diagnosis and 3 months after first SRE. Median survival in patients who did not experience SREs was 5 months. Among patients who received zoledronic acid before the first SRE, the median time to appearance of first SRE was significantly prolonged compared to control (7 months vs 4 months for control; P: 0.0005). Conclusions To our knowledge, this retrospective analysis is the largest multicenter study to demonstrate that bone metastases from GC are not so rare, are commonly aggressive and result in relatively early onset of SREs in the majority of patients. Indeed, our large study, which included 90 patients treated with ZOL, showed, for the first time in literature, a significant extension of time to first SRE and increase in the median survival time after diagnosis of bone metastasis. Taken together, these data may support the beneficial effects of ZOL in GC patients. PMID:24204569

  13. Nonalcoholic Fatty Liver Disease is Associated with Low Bone Mineral Density in Obese Children

    PubMed Central

    Pardee, Perrie E.; Dunn, Winston; Schwimmer, Jeffrey B.

    2015-01-01

    SUMMARY BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children. Liver disease can be a cause of low bone mineral density. Whether NAFLD influences bone health is unknown. AIM To evaluate bone mineral density in obese children with and without NAFLD. METHODS Thirty-eight children with biopsy-proven NAFLD were matched for age, sex, race, ethnicity, height, and weight to children without evidence of liver disease from the National Health and Nutrition Examination Survey. Bone mineral density was measured by dual energy x-ray absorptiometry. Age and sex-specific bone mineral density Z-scores were calculated and compared between children with and without NAFLD. After controlling for age, sex, race, ethnicity, and total percent body fat, the relationship between bone mineral density and the severity of histology was analyzed in children with NAFLD. RESULTS Obese children with NAFLD had significantly (p<0.0001) lower bone mineral density Z-scores (−1.98) than obese children without NAFLD (0.48). Forty-five percent of children with NAFLD had low bone mineral density for age, compared to none of the children without NAFLD (p < 0.0001). Among those children with NAFLD, children with NASH had a significantly (p< 0.05) lower bone mineral density Z-score (−2.37) than children with NAFLD who did not have NASH (−1.58). CONCLUSIONS NAFLD was associated with poor bone health in obese children. More severe disease was associated with lower bone mineralization. Further studies are needed to evaluate the underlying mechanisms and consequences of poor bone mineralization in children with NAFLD. PMID:22111971

  14. Bone mineral disorder in chronic kidney disease: Klotho and FGF23; cardiovascular implications.

    PubMed

    Salanova Villanueva, Laura; Sánchez González, Carmen; Sánchez Tomero, José Antonio; Aguilera, Abelardo; Ortega Junco, Esther

    2016-01-01

    Cardiovascular factors are one of the main causes of morbidity and mortality in patients with chronic kidney disease. Bone mineral metabolism disorders and inflammation are pathological conditions that involve increased cardiovascular risk in chronic kidney disease. The cardiovascular risk involvement of bone mineral metabolism classical biochemical parameters such as phosphorus, calcium, vitamin D and PTH is well known. The newest markers, FGF23 and klotho, could also be implicated in cardiovascular disease.

  15. Bone

    NASA Astrophysics Data System (ADS)

    Helmberger, Thomas K.; Hoffmann, Ralf-Thorsten

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

  16. 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

  17. Burden of metastatic bone disease from genitourinary malignancies.

    PubMed

    Mulders, Peter F; Abrahamsson, Per-Anders; Bukowski, Ronald M

    2010-11-01

    Bone metastases are common among patients with stage IV genitourinary cancers. Most patients with bone metastases develop at least one debilitating and potentially life-limiting skeletal-related event. These events are associated with increased medical expenses and decreased quality of life. Current guidelines recommend screening for bone metastases in men with high-risk prostate cancer, but guidance for screening and treatment of bone metastases from genitourinary cancers varies by country and setting. Several bisphosphonates have been evaluated in the advanced genitourinary cancer setting. Zoledronic acid has demonstrated efficacy in significantly reducing the risk of skeletal-related events in patients with bone metastases from a broad range of solid tumors including prostate, renal and bladder cancers, and is recommended for preserving bone health.

  18. Bone disease in cystic fibrosis: new pathogenic insights opening novel therapies.

    PubMed

    Jacquot, J; Delion, M; Gangloff, S; Braux, J; Velard, F

    2016-04-01

    Mutations within the gene encoding for the chloride ion channel cystic fibrosis transmembrane conductance regulator (CFTR) results in cystic fibrosis (CF), the most common lethal autosomal recessive genetic disease that causes a number of long-term health problems, as the bone disease. Osteoporosis and increased vertebral fracture risk associated with CF disease are becoming more important as the life expectancy of patients continues to improve. The etiology of low bone density is multifactorial, most probably a combination of inadequate peak bone mass during puberty and increased bone losses in adults. Body mass index, male sex, advanced pulmonary disease, malnutrition and chronic therapies are established additional risk factors for CF-related bone disease (CFBD). Consistently, recent evidence has confirmed that CFTR plays a major role in the osteoprotegerin (OPG) and COX-2 metabolite prostaglandin E2 (PGE2) production, two key regulators in the bone formation and regeneration. Several others mechanisms were also recognized from animal and cell models contributing to malfunctions of osteoblast (cell that form bone) and indirectly of bone-resorpting osteoclasts. Understanding such mechanisms is crucial for the development of therapies in CFBD. Innovative therapeutic approaches using CFTR modulators such as C18 have recently shown in vitro capacity to enhance PGE2 production and normalized the RANKL-to-OPG ratio in human osteoblasts bearing the mutation F508del-CFTR and therefore potential clinical utility in CFBD. This review focuses on the recently identified pathogenic mechanisms leading to CFBD and potential future therapies for treating CFBD.

  19. Bone marrow scintigraphy and computed tomography in myloproliferative disease

    SciTech Connect

    Goldsmith, S.J.; Gilbert, H.S.; Hermann, G.

    1985-05-01

    Peripheral bone marrow (BM) expansion in myeloproliferative disease (MPD) is demonstrated by scintigraphy (scint) with Technetium 99m sulfur colloid (TSC) or Indium III chloride (In). Computed tomography (CT) of the normal adult medullary cavity yields negative attenuation coefficients (AC) which become positive when BM fat is replaced. BM scint and CT of the medullary cavity are obtained in 23 studies in 21 pts: 6 polycythemia vera (PCV), 6 post PCV myeloid metaplasis (MyM), 4 agnogenic MyM, 3 myelodysplasia with refractory anemia, 1 acute myelocytic leukemia and 1 chronic myelocytic with acute leukemic transformation. AC were measured for BM cavity of lower extremities at each third of the femur and tibia. Values ranged from -89 to +289 Hounsfield units. The results are presented in this paper. There was agreement between SCINT and CT in 83% pts and segments. 80% of MB segments with + AC had scint identified BM. BM biopsy of the iliac crest demonstrated fibrosis or blast proliferation in pts with +AC rather than hypercellularity or osteosclerosis. The highest AC values (>200) were seen in pts with blast proliferation and fibrosis. Decreased BM scint visualization and +CT AC correlated with BM fibrosis and may reflect replacement of BM elements or decreased RES function. BM scint and CT are useful to monitor MPD and select BM sites for biopsy.

  20. Infrared imaging microscopy of bone: Illustrations from a mouse model of Fabry disease

    PubMed Central

    Boskey, Adele L.; Goldberg, Michel; Kulkarni, Ashok; Gomez, Santiago

    2006-01-01

    Bone is a complex tissue whose composition and properties vary with age, sex, diet, tissue type, health and disease. In this review, we demonstrate how infrared spectroscopy and infrared spectroscopic imaging can be applied to the study of these variations. A specific example of mice with Fabry disease (a lipid storage disease) is presented in which it is demonstrated that the bones of these young animals, while showing typical spatial variation in mineral content, mineral crystal size, and collagen maturity, do not differ from the bones of age- and sex-matched wild type animals. PMID:16697974

  1. The association of chronic kidney disease-mineral bone disorder and cardiovascular risk.

    PubMed

    Eddington, Helen; Kalra, Philip A

    2010-05-01

    Chronic kidney disease-mineral bone disorder (CKD-MBD) is a multifaceted definition used to help describe the systemic derangement of mineral bone metabolism in renal disease. This was previously referred to, rather simplistically, as 'renal osteodystrophy' or 'renal bone disease'. In this review, we will try to show the evidence relating these factors to cardiovascular morbidity and mortality and give some evidence as to the mechanisms for this. The treatments used for this condition are also integral to the increased cardiovascular mortality seen in renal patients and a summary of these effects will also be covered.

  2. Clinical utility of (18)F-fluoride PET/CT in benign and malignant bone diseases.

    PubMed

    Li, Yuxin; Schiepers, Christiaan; Lake, Ralph; Dadparvar, Simin; Berenji, Gholam R

    2012-01-01

    (18)F labeled sodium fluoride is a positron-emitting, bone seeking agent with more favorable skeletal kinetics than conventional phosphate and diphosphonate compounds. With the expanding clinical usage of PET/CT, there is renewed interest in using (18)F-fluoride PET/CT for imaging bone diseases. Growing evidence indicates that (18)F fluoride PET/CT offers increased sensitivity, specificity, and diagnostic accuracy in evaluating metastatic bone disease compared to (99m)Tc based bone scintigraphy. National Oncologic PET Registry (NOPR) has expanded coverage for (18)F sodium fluoride PET scans since February 2011 for the evaluation of osseous metastatic disease. In this article, we reviewed the pharmacological characteristics of sodium fluoride, as well as the clinical utility of PET/CT using (18)F-fluoride in both benign and malignant bone disorders.

  3. Bone Allografts: What Is the Risk of Disease Transmission with Bone Allografts?

    MedlinePlus

    ... Safety of Bone Allografts Used in Dentistry: A Review. JADA September 2008 vol. 139 no. 9 1192–1199. Mellonig JT. Donor selection, testing, and inactivation of the HIV virus in freeze-dried bone allografts. Pract Periodontics Aesthet Dent 1995;7:13–22. Mellonig JT, Prewett AB, Moyer ...

  4. Nuclear chromatin-concentrated osteoblasts in renal bone diseases.

    PubMed

    Kazama, Junichiro James; Yamamoto, Suguru; Narita, Ichiei; Kurihara, Satoshi

    2011-06-01

    The morphological appearance of an osteoblast largely alters with its differentiation and maturation, along with the change of cell function. We quantitatively observed the osteoblast morphology and compared it with bone metabolism. Biopsied iliac bone samples obtained from 77 dialysis patients (14 mild change, 37 osteitis fibrosa, 2 osteomalacia, 8 mixed, and 16 adynamic bone) were included in the study. Osteoblast appearances were classified into three groups: (i) type II and III osteoblasts, namely, active osteoblasts characterized by cuboidal or columnar shapes with or without a nuclear clear zone; (ii) type IV osteoblasts, lining osteoblasts characterized by extremely thin cytoplasm; and (iii) type V osteoblasts, apoptotic osteoblasts characterized by nuclear chromatin concentration. The results were quantitatively expressed as the length of bone surface covered by each type of osteoblasts. The type II and III osteoblasts were predominant in osteitis fibrosa, mixed, and mild change. The type IV osteoblasts were overwhelmingly predominant in adynamic bone. The type V osteoblasts appeared most frequently in osteitis fibrosa, followed by mixed and mild change. Both absolute and relative lengths of bone surface covered by the type V osteoblasts were significantly higher in the high-turnover bone group (osteitis fibrosa and mixed) than the low-turnover bone group (adynamic bone and osteomalacia). The type V osteoblasts were slightly correlated with serum intact parathyroid hormone levels. In conclusion, a high bone-turnover condition seems to be associated with the promotion of osteoblastic apoptosis in dialysis patients. This finding may explain the fact that osteopenia develops faster in CKD patients with high turnover of bone.

  5. Role of sclerostin in bone and cartilage and its potential as a therapeutic target in bone diseases

    PubMed Central

    2014-01-01

    Sclerostin is a small protein expressed by the SOST gene in osteocytes, bone cells that respond to mechanical stress applied to the skeleton and appear to play an important role in the regulation of bone remodeling. When sclerostin binds to its receptors on the cell surface of osteoblasts, a downstream cascade of intracellular signaling is initiated, with the ultimate effect of inhibiting osteoblastic bone formation. Recent studies have shown that the SOST gene is also expressed by articular chondrocytes and that modulation of its activity may have effects on articular cartilage and subchondral bone. The role of sclerostin in the pathogenesis of osteoarthritis in humans has not yet been defined, and the potential utility of treating osteoarthritis with interventions that alter sclerostin is not known. Rare genetic skeletal disorders in humans with low sclerostin levels, such as sclerosteosis and van Buchem disease, have been associated with a high bone mineral density (BMD) phenotype and low risk of fractures. This has led to the concept that antisclerostin interventions might be useful in the treatment of patients with osteoporosis and skeletal disorders associated with low bone mass. Compounds that inhibit sclerostin have been shown to stimulate bone formation and reduce bone resorption, with a robust increase in BMD. Investigational monoclonal antibodies to sclerostin, including romosozumab, blosozumab, and BPS804, have advanced to phase II clinical trials or beyond. If antisclerostin therapy is found to have beneficial effects on clinical endpoints, such as reduction of fracture risk or improvement in quality of life in patients with osteoarthritis, with a favorable balance of benefit and risk, then this class of compounds may become a prominent addition to the options for therapy of osteoporosis and other skeletal disorders. PMID:24688605

  6. Bone mineral density in glycogen storage disease type Ia and Ib.

    PubMed

    Minarich, Laurie A; Kirpich, Alexander; Fiske, Laurie M; Weinstein, David A

    2012-04-05

    Purpose:The aim of this study was to characterize the pathogenesis of low bone mineral density in glycogen storage disease type Ia and Ib.Methods:A retrospective chart review performed at the University of Florida Glycogen Storage Disease Program included patients with glycogen storage disease type Ia and Ib for whom dual-energy X-ray absorptiometry analysis was performed. A Z-score less than -2 SD was considered low. Analysis for association of bone mineral density with age, gender, presence of complications, mean triglyceride and 25-hydroxyvitamin D concentrations, erythrocyte sedimentation rate, duration of granulocyte colony-stimulating factor therapy, and history of corticosteroid use was performed.Results:In glycogen storage disease Ia, 23/42 patients (55%) had low bone mineral density. Low bone mineral density was associated with other disease complications (P = 0.02) and lower mean serum 25-hydroxyvitamin D concentration (P = 0.03). There was a nonsignificant trend toward lower mean triglyceride concentration in the normal bone mineral density group (P = 0.1).In patients with glycogen storage disease type Ib, 8/12 (66.7%) had low bone mineral density. We did not detect an association with duration of granulocyte colony-stimulating factor therapy (P = 0.68), mean triglyceride level (P = 0.267), erythrocyte sedimentation rate (P = 0.3), or 25-hydroxyvitamin D (P = 0.63) concentration, and there was no evidence that corticosteroid therapy was associated with lower bone mineral density (P = 1).Conclusion:In glycogen storage disease type Ia, bone mineral density is associated with other complications and 25-hydroxyvitamin D status. In glycogen storage disease type Ib, bone mineral density was not associated with any covariates analyzed, suggesting multifactorial etiology or reflecting a small sample.Genet Med advance online publication 5 April 2012.

  7. Recurrent infarction of sphenoid bone with subperiosteal collection in a child with sickle cell disease.

    PubMed

    Alsuhaibani, Adel H; Marzouk, Mohammed Abu

    2011-01-01

    Infarction of the orbital bone in patients with sickle cell disease is very rare. The authors report a young boy who presented twice with marked acute proptosis and eyelid swelling of the right eye resulting from infarction in the greater wing of the sphenoid bone accompanied by an orbital subperiosteal collection. The time interval between the 2 attacks was 3 years.

  8. Myeloid-derived suppressor cells as a novel target for the control of osteolytic bone disease.

    PubMed

    Sawant, Anandi; Ponnazhagan, Selvarangan

    2013-05-01

    Myeloid-derived suppressor cells (MDSC) from mice bearing bone metastases differentiate into functional osteoclasts in vitro and in vivo, through a signaling pathway that relies on nitric oxide. In addition, MDSC-targeting drugs have been shown to robustly inhibit osteolysis. Thus, MDSC stand out as novel osteoclast progenitors and hence as candidate targets for the control of osteolytic bone disease.

  9. Generalized metabolic bone disease in Neurofibromatosis type I

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Skeletal abnormalities are a recognized component of Neurofibromatosis type I (NF1), but a generalized metabolic bone defect in NF1 has not been fully characterized thus far. The purpose of this study was to characterize at the densitometric, biochemical, and pathological level the bone involvement ...

  10. Predictive factors for skeletal complications in hormone-refractory prostate cancer patients with metastatic bone disease

    PubMed Central

    Berruti, A; Tucci, M; Mosca, A; Tarabuzzi, R; Gorzegno, G; Terrone, C; Vana, F; Lamanna, G; Tampellini, M; Porpiglia, F; Angeli, A; Scarpa, R M; Dogliotti, L

    2005-01-01

    Factors predictive of skeletal-related events (SREs) in bone metastatic prostate cancer patients with hormone-refractory disease were investigated. We evaluated the frequency of SREs in 200 hormone-refractory patients consecutively observed at our Institution and followed until death or the last follow-up. Baseline parameters were evaluated in univariate and multivariate analysis as potential predictive factors of SREs. Skeletal-related events were observed in 86 patients (43.0%), 10 of which (5.0%) occurred before the onset of hormone-refractory disease. In univariate analysis, patient performance status (P=0.002), disease extent (DE) in bone (P=0.0001), bone pain (P=0.0001), serum alkaline phosphatase (P=0.0001) and urinary N-telopeptide of type one collagen (P=0.0001) directly correlated with a greater risk to develop SREs, whereas Gleason score at diagnosis, serum PSA, Hb, serum albumin, serum calcium, types of bone lesions and duration of androgen deprivation therapy did not. Both DE in bone (hazard ratio (HR): 1.16, 95% confidence interval (CI): 1.07–1.25, P=0.000) and pain score (HR: 1.13, 95% CI: 1.06–1.20, P=0.000) were independent variables predicting for the onset of SREs in multivariate analysis. In patients with heavy tumour load in bone and great bone pain, the percentage of SREs was almost twice as high as (26 vs 52%, P<0.02) and occurred significantly earlier (P=0.000) than SREs in patients with limited DE in bone and low pain. Bone pain and DE in bone independently predict the occurrence of SREs in bone metastatic prostate cancer patients with hormone-refractory disease. These findings could help physicians in tailoring the skeletal follow-up most appropriate to individual patients and may prove useful for stratifying patients enrolled in bisphosphonate clinical trials. PMID:16222309

  11. [Modulation of transcriptional regulation during bone and cartilage development and their disease].

    PubMed

    Nishimura, Riko; Hata, Kenji; Takashima, Rikako; Yoshida, Michiko; Nakamura, Eriko; Kida, Junpei; Yagi, Hiroko

    2013-11-01

    Genetic and biochemical studies have identified transcription factors critical and specific for bone and cartilage development. More recent studies revealed the molecular mechanisms how these transcription factors regulate bone and cartilage development. Especially, we appreciate recent advances in molecular function of the complex assembled by these transcription factors and epigenetic regulation of them. Aging, inflammation, biological stress, and disorder of endocrine system induce several bone and/or cartilage diseases by affecting the transcriptional and epigenetic regulation. In this review, we would like to describe the transcriptional and epigenetic regulation during developmental and pathological stages. In addition, we discuss possible application of these information in regeneration of bone and cartilage.

  12. Can acetazolamide be used to treat diseases involving increased bone mineral density?

    PubMed Central

    González-Rodríguez, Juan David; Luis-Yanes, María Isabel; Inglés-Torres, Esther; Arango-Sancho, Pedro; Cabrera-Sevilla, José Eugenio; Duque-Fernández, María Rosario; Gil-Sánchez, Salvador; García-Nieto, Víctor Manuel

    2016-01-01

    Summary Sclerosing bone dysplasias are a series of clinically and genetically heterogeneous diseases characterized by functional failure of the osteoclasts in bone resorption, leading to an excessive amount of bone mineral density (BMD) which could have serious clinical consequences. We treated three children affected with seriously high levels of BMD with acetazolamide, with the intention of inducing metabolic acidosis, thus increasing bone resorption and reducing BMD. All our patients tolerated and followed the treatment well and the clinical response was satisfactory in all cases. PMID:27904825

  13. Development, validation and characterization of a novel mouse model of Adynamic Bone Disease (ABD).

    PubMed

    Ng, Adeline H; Willett, Thomas L; Alman, Benjamin A; Grynpas, Marc D

    2014-11-01

    The etiology of Adynamic Bone Disease (ABD) is poorly understood but the hallmark of ABD is a lack of bone turnover. ABD occurs in renal osteodystrophy (ROD) and is suspected to occur in elderly patients on long-term anti-resorptive therapy. A major clinical concern of ABD is diminished bone quality and an increased fracture risk. To our knowledge, experimental animal models for ABD other than ROD-ABD have not been developed or studied. The objectives of this study were to develop a mouse model of ABD without the complications of renal ablation, and to characterize changes in bone quality in ABD relative to controls. To re-create the adynamic bone condition, 4-month old female Col2.3Δtk mice were treated with ganciclovir to specifically ablate osteoblasts, and pamidronate was used to inhibit osteoclastic resorption. Four groups of animals were used to characterize bone quality in ABD: Normal bone controls, No Formation controls, No Resorption controls, and an Adynamic group. After a 6-week treatment period, the animals were sacrificed and the bones were harvested for analyses. Bone quality assessments were conducted using established techniques including bone histology, quantitative backscattered electron imaging (qBEI), dual energy X-ray absorptiometry (DXA), microcomputed tomography (microCT), and biomechanical testing. Histomorphometry confirmed osteoblast-related hallmarks of ABD in our mouse model. Bone formation was near complete suppression in the No Formation and Adynamic specimens. Inhibition of bone resorption in the Adynamic group was confirmed by tartrate-resistant acid phosphatase (TRAP) stain. Normal bone mineral density and architecture were maintained in the Adynamic group, whereas the No Formation group showed a reduction in bone mineral content and trabecular thickness relative to the Adynamic group. As expected, the No Formation group had a more hypomineralized profile and the Adynamic group had a higher mean mineralization profile that is

  14. Moderate chronic kidney disease impairs bone quality in C57Bl/6J mice.

    PubMed

    Heveran, Chelsea M; Ortega, Alicia M; Cureton, Andrew; Clark, Ryan; Livingston, Eric W; Bateman, Ted A; Levi, Moshe; King, Karen B; Ferguson, Virginia L

    2016-05-01

    Chronic kidney disease (CKD) increases bone fracture risk. While the causes of bone fragility in CKD are not clear, the disrupted mineral homeostasis inherent to CKD may cause material quality changes to bone tissue. In this study, 11-week-old male C57Bl/6J mice underwent either 5/6th nephrectomy (5/6 Nx) or sham surgeries. Mice were fed a normal chow diet and euthanized 11weeks post-surgery. Moderate CKD with high bone turnover was established in the 5/6 Nx group as determined through serum chemistry and bone gene expression assays. We compared nanoindentation modulus and mineral volume fraction (assessed through quantitative backscattered scanning electron microscopy) at matched sites in arrays placed on the cortical bone of the tibia mid-diaphysis. Trabecular and cortical bone microarchitecture and whole bone strength were also evaluated. We found that moderate CKD minimally affected bone microarchitecture and did not influence whole bone strength. Meanwhile, bone material quality decreased with CKD; a pattern of altered tissue maturation was observed with 5/6 Nx whereby the newest 60μm of bone tissue adjacent to the periosteal surface had lower indentation modulus and mineral volume fraction than more interior, older bone. The variance of modulus and mineral volume fraction was also altered following 5/6 Nx, implying that tissue-scale heterogeneity may be negatively affected by CKD. The observed lower bone material quality may play a role in the decreased fracture resistance that is clinically associated with human CKD.

  15. National Institutes of Health Osteoporosis and Related Bone Diseases~National Resource Center

    MedlinePlus

    ... Publications View Publications View Publications View Publications Research Resources Clinical Trials www.clinicaltrials.gov MedlinePlus www.nlm. ... The NIH Osteoporosis and Related Bone Diseases ~ National Resource Center is supported by the National Institute of ...

  16. What is the optimal bone-preserving strategy for patients with Addison's disease?

    PubMed

    Lee, Paul; Greenfield, Jerry R

    2015-08-01

    Addison's disease is associated with low bone mineral density and increased risk of hip fractures. Causes are multifactorial, contributed by underlying adrenocortical hormonal deficiency, associated autoimmune endocrinopathies, electrolyte disturbances and, in some patients, supraphysiologic glucocorticoid replacement. Recent realization of physiologic cortisol production rate has revised downwards glucocorticoid replacement dosages. Meanwhile, new research has emerged suggesting complex interplay between sodium and calcium homoeostasis under the influence of mineralocorticoid and parathyroid hormone that may impact bone health. As the prevalence of Addison's disease is rising, and osteoporosis and fractures are associated with significant morbidity and increased mortality, attention to bone preservation in Addison's disease is of clinical relevance and importance. We suggest an approach to bone health in Addison's disease integrating physiologic adrenocortical hormonal replacement with electrolyte and mineral homoeostasis optimization.

  17. Wnt signaling and potential applications in bone diseases.

    PubMed

    Rawadi, Georges

    2008-07-01

    In the United States, it is estimated that $10-15 billion is spent annually for the treatment of osteoporotic fracture. The worldwide annual incidence of osteoporotic hip fracture exceeds 1.7 million cases. Bone loss leading to osteoporosis and osteoporotic fractures are caused by an imbalance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption and numerous factors have been implicated in the development of osteoporosis. The prevention and treatment of osteoporosis traditionally involves the use of anti-resorptive agents, which target osteoclast function, but do not lead to a significant increase in bone mass and therefore only partially reduce risk of fractures. For these reasons, the search for anabolic agents, which target osteoblast function, represents an urgent medical need. Genetic studies have firmly established a link between bone mass in humans and Wnt signaling. Multiple genetic and pharmacological manipulations of Wnt signaling in mice have since then confirmed the central role of this pathway in regulating bone formation. The existence of many potential pharmacological targets in this pathway makes it attractive for bone anabolic drug discovery.

  18. Osteoblast dysfunctions in bone diseases: from cellular and molecular mechanisms to therapeutic strategies.

    PubMed

    Marie, Pierre J

    2015-04-01

    Several metabolic, genetic and oncogenic bone diseases are characterized by defective or excessive bone formation. These abnormalities are caused by dysfunctions in the commitment, differentiation or survival of cells of the osteoblast lineage. During the recent years, significant advances have been made in our understanding of the cellular and molecular mechanisms underlying the osteoblast dysfunctions in osteoporosis, skeletal dysplasias and primary bone tumors. This led to suggest novel therapeutic approaches to correct these abnormalities such as the modulation of WNT signaling, the pharmacological modulation of proteasome-mediated protein degradation, the induction of osteoprogenitor cell differentiation, the repression of cancer cell proliferation and the manipulation of epigenetic mechanisms. This article reviews our current understanding of the major cellular and molecular mechanisms inducing osteoblastic cell abnormalities in age-related bone loss, genetic skeletal dysplasias and primary bone tumors, and discusses emerging therapeutic strategies to counteract the osteoblast abnormalities in these disorders of bone formation.

  19. A rare variant of Caffey's disease - X-rays, bone scan and FDG PET findings.

    PubMed

    Agrawal, Archi; Purandare, Nilendu; Shah, Sneha; Rangarajan, Venkatesh

    2011-04-01

    An 18-month-old boy with history of fever of 4 months duration and with swelling of the limbs was referred for a bone scan. There were multiple swellings over his upper and lower limbs, with bowing of the lower limbs. His radiological skeletal survey revealed marked periosteal new bone formation surrounding the diaphysis of long bones. A bone scan done with 99m Tc-MDP showed diffusely increased tracer uptake in all the long bones. A fluorodeoxyglucose positron emission tomography (FDG PET) scan done to assess the metabolic activity showed patchy FDG uptake in the long bones, ankle joint and anterior ends of few ribs. His clinical and imaging findings led to the diagnosis of Caffey's disease.

  20. Assessment of metabolic bone diseases by quantitative computed tomography

    NASA Technical Reports Server (NTRS)

    Richardson, M. L.; Genant, H. K.; Cann, C. E.; Ettinger, B.; Gordan, G. S.; Kolb, F. O.; Reiser, U. J.

    1985-01-01

    Advances in the radiologic sciences have permitted the development of numerous noninvasive techniques for measuring the mineral content of bone, with varying degrees of precision, accuracy, and sensitivity. The techniques of standard radiography, radiogrammetry, photodensitometry, Compton scattering, neutron activation analysis, single and dual photon absorptiometry, and quantitative computed tomography (QCT) are described and reviewed in depth. Results from previous cross-sectional and longitudinal QCT investigations are given. They then describe a current investigation in which they studied 269 subjects, including 173 normal women, 34 patients with hyperparathyroidism, 24 patients with steroid-induced osteoporosis, and 38 men with idiopathic osteoporosis. Spinal quantitative computed tomography, radiogrammetry, and single photon absorptiometry were performed, and a spinal fracture index was calculated on all patients. The authors found a disproportionate loss of spinal trabecular mineral compared to appendicular mineral in the men with idiopathic osteoporosis and the patients with steroid-induced osteoporosis. They observed roughly equivalent mineral loss in both the appendicular and axial regions in the hyperparathyroid patients. The appendicular cortical measurements correlated moderately well with each other but less well with spinal trabecular QCT. The spinal fracture index correlated well with QCT and less well with the appendicular measurements. Knowledge of appendicular cortical mineral status is important in its own right but is not a valid predictor of axial trabecular mineral status, which may be disproportionately decreased in certain diseases. Quantitative CT provides a reliable means of assessing the latter region of the skeleton, correlates well with the spinal fracture index (a semiquantitative measurement of end-organ failure), and offers the clinician a sensitive means of following the effects of therapy.

  1. Kuhlmann vascularized bone grafting for treatment of Kienböck's disease: a case report

    PubMed Central

    Sbai, Mohamed Ali; Msek, Hichem; Benzarti, Sofien; Boussen, Monia; Maalla, Riadh

    2016-01-01

    Treatment of Kienböck's disease has historically been determined by staging, ulnar variance, and presence or absence of arthritic changes. With the advent of newer techniques of vascularized bone grafting, the status of the cartilage shell of the lunate has become another factor that can influence the procedure performed. The purpose of this article is to describe the technique of Kuhlmann vascularized bone graft for Kienböck's disease. In addition, the indications, contraindications, and outcomes are described. PMID:27583101

  2. Kuhlmann vascularized bone grafting for treatment of Kienböck's disease: a case report.

    PubMed

    Sbai, Mohamed Ali; Msek, Hichem; Benzarti, Sofien; Boussen, Monia; Maalla, Riadh

    2016-01-01

    Treatment of Kienböck's disease has historically been determined by staging, ulnar variance, and presence or absence of arthritic changes. With the advent of newer techniques of vascularized bone grafting, the status of the cartilage shell of the lunate has become another factor that can influence the procedure performed. The purpose of this article is to describe the technique of Kuhlmann vascularized bone graft for Kienböck's disease. In addition, the indications, contraindications, and outcomes are described.

  3. Current perspectives on bisphosphonate treatment in Paget’s disease of bone

    PubMed Central

    Wat, Winnie Zee Man

    2014-01-01

    Paget’s disease of bone is a chronic metabolic bone disease with focal increase in bone turnover. The exact etiology of the disease is uncertain, although genetic and environmental factors are believed to be important. Bisphosphonate is the main class of medication being used to control disease activity via its antiresorptive effect. This review discusses the controversies concerning the use of bisphosphonates in the treatment of Paget’s disease of bone, the efficacy of different bisphosphonates in controlling disease activity, and the possible rare side effects of bisphosphonates. Symptoms are the main indication for treatment in Paget’s disease of bone. As treatment benefits in asymptomatic individuals remain controversial and nonevidence based, the decision to treat these patients should be individualized to their risk and benefit profiles. There are several trials conducted to evaluate and compare the efficacy of different regimes of bisphosphonates for treating Paget’s disease of bone. Most trials used biochemical markers rather than clinical symptoms or outcomes as parameters for comparison. Zoledronate is an attractive option as it can achieve high rates of biochemical remission and sustain long duration of suppression by a single dose. Atypical femoral fracture and osteonecrosis of the jaw are two rare and severe side effects reported, possibly related to the use of bisphosphonates in patients with osteoporosis and malignancy-induced hypercalcemia. As the regimes of bisphosphonates used for treating Paget’s disease of bone are different from those two diseases, the risks of developing these two possible side effects are expected to be very low, although this remains unknown. Vitamin D and calcium supplement should be given to patients at risk of vitamin D insufficiency when given zoledronate, as symptomatic hypocalcemia may develop. For those intolerant of bisphosphonates, subcutaneous calcitonin can be used for a limited period due to its

  4. Modeling failure in brittle porous ceramics

    NASA Astrophysics Data System (ADS)

    Keles, Ozgur

    Brittle porous materials (BPMs) are used for battery, fuel cell, catalyst, membrane, filter, bone graft, and pharmacy applications due to the multi-functionality of their underlying porosity. However, in spite of its technological benefits the effects of porosity on BPM fracture strength and Weibull statistics are not fully understood--limiting a wider use. In this context, classical fracture mechanics was combined with two-dimensional finite element simulations not only to account for pore-pore stress interactions, but also to numerically quantify the relationship between the local pore volume fraction and fracture statistics. Simulations show that even the microstructures with the same porosity level and size of pores differ substantially in fracture strength. The maximum reliability of BPMs was shown to be limited by the underlying pore--pore interactions. Fracture strength of BMPs decreases at a faster rate under biaxial loading than under uniaxial loading. Three different types of deviation from classic Weibull behavior are identified: P-type corresponding to a positive lower tail deviation, N-type corresponding to a negative lower tail deviation, and S-type corresponding to both positive upper and lower tail deviations. Pore-pore interactions result in either P-type or N-type deviation in the limit of low porosity, whereas S-type behavior occurs when clusters of low and high fracture strengths coexist in a fracture data.

  5. Bone disease in patients with long-term renal transplantation and normal renal function.

    PubMed

    Carlini, R G; Rojas, E; Weisinger, J R; Lopez, M; Martinis, R; Arminio, A; Bellorin-Font, E

    2000-07-01

    Renal osteodystrophy may persist during the early years after renal transplantation. However, information on bone status after a successful long-term renal transplantation is limited. We examined biochemical parameters, bone mineral density (BMD), and bone histomorphometry in 25 asymptomatic men with normal renal function after 7.5 +/- 5.7 years of a renal transplantation. Serum calcium, phosphorus, alkaline phosphatase, and 1,25(OH)(2)D(3) levels and urinary calcium level and cyclic andenosine monophosphate excretion were within normal range in all patients. Serum intact parathyroid hormone (PTH) level was elevated in 11 subjects (133.6 +/- 78 pg/mL) and normal in the other 14 subjects (47.9 +/- 13.6 pg/mL). Mean BMD at the lumbar spine and femoral neck was low in the entire group. However, it progressively increased as time after transplantation increased, approaching normal values after 10 years. Bone histomorphometric analysis showed bone resorption, osteoid volume, and osteoid surface greater than normal range in the majority of patients. Bone formation rate and mineralization surface were low, and mineralization time was delayed in most patients. These lesions were more severe in patients after 3 to 4 years of transplantation but improved with time and approached normal values after a period of 10 years. PTH values did not correlate with bone histological characteristics or BMD. These results show that the bone alterations observed after long-term renal transplantation consist of a mixed bone disease in which features of high bone turnover coexist with altered bone formation and delayed mineralization. These findings may result from the combined effect of preexisting bone disease and immunosuppressive therapy.

  6. Interventional Radiologist's perspective on the management of bone metastatic disease.

    PubMed

    Cazzato, R L; Buy, X; Grasso, R F; Luppi, G; Faiella, E; Quattrocchi, C C; Pantano, F; Beomonte Zobel, B; Tonini, G; Santini, D; Palussiere, J

    2015-08-01

    Bone metastases can be treated by interventional radiologists with a minimally invasive approach. Such treatments are performed percutaneously under radiological imaging guidance. Different interventional techniques can be applied with curative or palliative intent depending on lesions and patients' status. In the whole, available interventional techniques are distinguished into "ablative" and "consolidative". Ablative techniques achieve bone tumor necrosis by dramatically increasing or decreasing intra-tumoral temperature. This option can be performed in order to alleviate pain or to eradicate the lesion. On the other hand, consolidative techniques aim at obtaining bone defect reinforcement mainly to alleviate pain and prevent pathological fractures. We herein present evidence supporting the application of each different interventional technique, as well as common strategies followed by interventional radiologists while approaching bone metastases.

  7. Bone and mineral metabolism in adult celiac disease

    SciTech Connect

    Caraceni, M.P.; Molteni, N.; Bardella, M.T.; Ortolani, S.; Nogara, A.; Bianchi, P.A.

    1988-03-01

    Bone mineral density (/sup 125/I photon absorptiometry) was lower in 20 untreated adult celiac patients than in sex- and age-matched controls (p less than 0.001), and plasma alkaline phosphatase, parathyroid hormone, urinary hydroxyproline/creatinine levels were higher than normal (p less than 0.05, less than 0.001, less than 0.05, respectively). Gluten-free diet was started, and the patients were divided randomly into two treatment groups, one which received oral 25-hydroxyvitamin D 50 micrograms/day and one which did not. After 12 months' treatment, bone turnover markers showed a decrease, which did not reach statistical significance, and bone mineral density did not show significant modifications compared with base line in either group. It was found that a gluten-free diet followed for 1 yr can prevent further bone loss, but no significant differences were detected between the two groups.

  8. Evaluation of the brittleness of the rocks using various brittleness indices

    NASA Astrophysics Data System (ADS)

    Cheon, Dae-Sung; Jung, Yong-Bok; Park, Chan; Park, Eui-Seob

    2015-04-01

    In general, the rock has the feature of drastically reduced bearing capacity during the small strain by the brittle characteristic. Because brittleness is considered as both of inherent property and behavior of materials, various brittleness indices have been proposed and based on these the brittleness degrees of the rock are determined. The brittleness indices are used for evaluating the stability of brittle failure in deep mines or underground excavations, drillability evaluation in the well drilling field, sawability evaluation in the building stone field and others. In recent years there has been utilized as a descriptor of the hydraulic fracturing in shale gas and enhanced geothermal system. In this paper, we estimated the brittleness index of different types of rocks using various brittleness indices proposed by previous researchers and investigated their relationship and applicability. The commonly used brittleness index in Rock Mechanics is the ratio between uniaxial compressive strength and tensile strength. In Reservior Geomechanics, the indices using dynamic elastic modulus and Poisson's ratio calculated from well logging data are generally used. In higher brittleness or brittleness index, the rock shows the following characteristics; low values of elongation of grains, fracture failure, formation of fines and debris, a higher ratio of compressive to tensile strength, higher resilience, higher internal friction angle, formation of cracks in indentation, easy to fracture etc.. The brittleness index showed relatively good relations with rock intrinsic properties such as uniaxial compressive strength, elastic modulus and fracture toughness in particular rock types. The correlation among brittleness index using geophysical logging data was shown. However, it was difficult to find a relationship of the brittleness indices between uses in traditional Rock Mechanics and Reservoir Geomechanics. Since some brittleness indices have no special meaning, a careful

  9. Treatment of chronic osteomyelitis secondary to hydatid disease of bone using gentamycin beads.

    PubMed

    Obeidat, Moutasem M; Mustafa, Ziad

    2012-09-01

    Hydatid disease of bone is rare. It remains asymptomatic over a long period. It is usually detected after a pathological fracture or secondary infection or following the onset of compressive myelopathy in cases of vertebral lesions. Secondary infection of hydatid disease of bone could be difficult to treat. The authors present a case of chronic osteomyelitis of the proximal aspect of the left femur in a 37-year-old male patient secondary to hydatid disease of bone. It was treated by aggressive debridement, gentamycin beads, and bone graft to fill the defect. No recurrence of the hydatid lesion or infection was detected after 2 years. This case showed that in addition to aggressive debridement, gentamycin beads may be valuable in eradicating the infection in such a case.

  10. Optimal management of bone mineral disorders in chronic kidney disease and ESRD

    PubMed Central

    Lundquist, Andrew L.; Nigwekar, Sagar U.

    2016-01-01

    Purpose of review This review summarizes recent studies on chronic kidney disease-mineral bone disorders, with a focus on new developments in disease management. Recent findings The term chronic kidney disease-mineral bone disorder has come to describe an increasingly complex network of alterations in minerals and skeletal disorders that contribute to the significant cardiovascular morbidity and mortality seen in patients with chronic kidney disease and ESRD. Clinical studies continue to suggest associations with clinical outcomes, yet current clinical trials have failed to support causality. Variability in practice exists as current guidelines for management of bone-mineral disorders are often based on weak evidence. Recent studies implicate novel pathways for therapeutic intervention in clinical trials. Summary Mineral-bone disorders in chronic kidney disease arise from alterations in a number of molecules in an increasingly complex physiological network interconnecting bone and the cardiovascular system. Despite extensive associations with improved outcomes in a number of molecules, clinical trials have yet to prove causality and there is an absence of new therapies available to improve patient outcomes. Additional clinical trials that can incorporate the complexity of mineral bone disorders and with the ability to intervene on more than one pathway are needed to advance patient care. PMID:26785065

  11. A virtual approach to evaluate therapies for management of multiple myeloma induced bone disease.

    PubMed

    Ji, Bing; Genever, Paul G; Fagan, Michael J

    2016-03-01

    Multiple myeloma bone disease is devastating for patients and a major cause of morbidity. The disease leads to bone destruction by inhibiting osteoblast activity while stimulating osteoclast activity. Recent advances in multiple myeloma research have improved our understanding of the pathogenesis of multiple myeloma-induced bone disease and suggest several potential therapeutic strategies. However, the effectiveness of some potential therapeutic strategies still requires further investigation and optimization. In this paper, a recently developed mathematical model is extended to mimic and then evaluate three therapies of the disease, namely: bisphosphonates, bortezomib and TGF-β inhibition. The model suggests that bisphosphonates and bortezomib treatments not only inhibit bone destruction, but also reduce the viability of myeloma cells. This contributes to the current debate as to whether bisphosphonate therapy has an anti-tumour effect. On the other hand, the analyses indicate that treatments designed to inhibit TGF-β do not reduce bone destruction, although it appears that they might reduce the viability of myeloma cells, which again contributes to the current controversy regarding the efficacy of TGF-β inhibition in multiple myeloma-induced bone disease.

  12. Preliminary results of automated removal of degenerative joint disease in bone scan lesion segmentation

    NASA Astrophysics Data System (ADS)

    Chu, Gregory H.; Lo, Pechin; Kim, Hyun J.; Auerbach, Martin; Goldin, Jonathan; Henkel, Keith; Banola, Ashley; Morris, Darren; Coy, Heidi; Brown, Matthew S.

    2013-03-01

    Whole-body bone scintigraphy (or bone scan) is a highly sensitive method for visualizing bone metastases and is the accepted standard imaging modality for detection of metastases and assessment of treatment outcomes. The development of a quantitative biomarker using computer-aided detection on bone scans for treatment response assessment may have a significant impact on the evaluation of novel oncologic drugs directed at bone metastases. One of the challenges to lesion segmentation on bone scans is the non-specificity of the radiotracer, manifesting as high activity related to non-malignant processes like degenerative joint disease, sinuses, kidneys, thyroid and bladder. In this paper, we developed an automated bone scan lesion segmentation method that implements intensity normalization, a two-threshold model, and automated detection and removal of areas consistent with non-malignant processes from the segmentation. The two-threshold model serves to account for outlier bone scans with elevated and diffuse intensity distributions. Parameters to remove degenerative joint disease were trained using a multi-start Nelder-Mead simplex optimization scheme. The segmentation reference standard was constructed manually by a panel of physicians. We compared the performance of the proposed method against a previously published method. The results of a two-fold cross validation show that the overlap ratio improved in 67.0% of scans, with an average improvement of 5.1% points.

  13. The pathophysiological role of PEDF in bone diseases.

    PubMed

    Broadhead, M L; Akiyama, T; Choong, P F M; Dass, C R

    2010-04-01

    First discovered in 1991 as a factor secreted by retinal pigment epithelial cells, the potency of pigment epithelium derived factor (PEDF) as an anti-angiogenic has led to examination of its role in active bone growth, repair and remodelling. In the musculoskeletal system, PEDF expression occurs particularly at sites of active bone formation. Expression has been noted in osteoblasts and to a lesser degree osteoclasts, the major classes of bone cells. In fact, PEDF is capable of inducing differentiation of precursor cells into mature osteoblasts. Expression and localisation are closely linked with that of vascular endothelial growth factor (VEGF). Studies at the epiphyseal plate have revealed that PEDF expression plays a key role in endochondral ossification, and beyond this may account for the epiphyseal plate's innate ability to resist neoplastic cell invasion. Collagen-1, the major protein in bone, is avidly bound by PEDF, implicating an important role played by this protein on PEDF function, possibly through MMP-2 and -9 activity. Surprisingly, the role of PEDF has not been evaluated more widely in bone disorders, so the challenge ahead lies in a more diverse evaluation of PEDF in various osteologic pathologies including osteoarthritis and fracture healing.

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

    SciTech Connect

    Garnero, P.; Delmas, P.D.

    1993-10-01

    The authors measured serum bone alkaline phosphatase (B-ALP) with a new immunoradiometric assay (IRMA) in a large sample of healthy controls comprising 173 women and 180 men, 20-88 yr of age, and in patients with metabolic bone disease. Using serum samples from patients with liver disease and patients with Paget's disease with elevated total alkaline phosphatase (T-ALP) as a source of, respectively, liver and bone isoenyzmes, they determined a liver cross-reactivity of the IRMA of 16% that was confirmed by electrophoresis of the circulating alkaline phosphatase isoenzymes. The IRMA was linear for serial sample dilutions, the recovery ranged from 89-110%, and the intra- and interassay variations were below 7% and 9%, respectively. B-ALP increased linearly with age in both sexes, and the mean B-ALP serum levels were not significantly different for women and men (11.3 [+-] 4.8 ng/mL for women; 11.0 [+-] 4.0 ng/mL for men). The increase in B-ALP after the menopause was significantly higher than that in T-ALP (+77% vs. +24%; P<0.001). When the values of postmenopausal women were expressed as the SD from the mean of premenopausal women, the mean Z scores were 2.2[+-] 1.8 for B-ALP and 0.9 [+-] 1.3 for T-ALP (P<0.001 between the two).

  15. [Bone and joint diseases in children. Effects of sports on bone and joint disorders during childhood].

    PubMed

    Uchio, Yuji; Matsusaki, Masahiko; Yamamoto, Soichiro; Kumahashi, Nobuyuki

    2010-06-01

    Recently, opposing trends have appeared to be either excessiveness or lack in the frequency of exercise or sports during childhood, both of which are believed to be associated with various sports-related injuries. In childhood, the bones, muscles, and ligaments are developing and not yet matured; though soft and flexible, their relative low strength is inadequate to tolerate abnormal external forces. Although a child's body normally has substantial self-healing ability, there is the risk of causing a lifelong deformity or growth disorder if not treated properly. A comprehensively organized system for the prevention, early detection, and treatment of bone and joint disorders in children should be developed in the future.

  16. TGF-β and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease

    PubMed Central

    Wu, Mengrui; Chen, Guiqian; Li, Yi-Ping

    2016-01-01

    Transforming growth factor-beta (TGF-β) and bone morphogenic protein (BMP) signaling has fundamental roles in both embryonic skeletal development and postnatal bone homeostasis. TGF-βs and BMPs, acting on a tetrameric receptor complex, transduce signals to both the canonical Smad-dependent signaling pathway (that is, TGF-β/BMP ligands, receptors, and Smads) and the non-canonical-Smad-independent signaling pathway (that is, p38 mitogen-activated protein kinase/p38 MAPK) to regulate mesenchymal stem cell differentiation during skeletal development, bone formation and bone homeostasis. Both the Smad and p38 MAPK signaling pathways converge at transcription factors, for example, Runx2 to promote osteoblast differentiation and chondrocyte differentiation from mesenchymal precursor cells. TGF-β and BMP signaling is controlled by multiple factors, including the ubiquitin–proteasome system, epigenetic factors, and microRNA. Dysregulated TGF-β and BMP signaling result in a number of bone disorders in humans. Knockout or mutation of TGF-β and BMP signaling-related genes in mice leads to bone abnormalities of varying severity, which enable a better understanding of TGF-β/BMP signaling in bone and the signaling networks underlying osteoblast differentiation and bone formation. There is also crosstalk between TGF-β/BMP signaling and several critical cytokines’ signaling pathways (for example, Wnt, Hedgehog, Notch, PTHrP, and FGF) to coordinate osteogenesis, skeletal development, and bone homeostasis. This review summarizes the recent advances in our understanding of TGF-β/BMP signaling in osteoblast differentiation, chondrocyte differentiation, skeletal development, cartilage formation, bone formation, bone homeostasis, and related human bone diseases caused by the disruption of TGF-β/BMP signaling. PMID:27563484

  17. Challenging the current approaches to multiple myeloma- and other cancer-related bone diseases: from bisphosphonates to targeted therapy.

    PubMed

    Kleber, Martina; Udi, Josefina; Metzke, Barbara; Terpos, Evangelos; Roodmann, G David; Morgan, Gareth; Dispenzieri, Angela; Einsele, Hermann; Wäsch, Ralph; Engelhardt, Monika

    2012-06-01

    An international myeloma meeting entitled "Challenging the current approaches to multiple myeloma- and other cancer-related bone diseases: from bisphosphonates to targeted therapy" was held in Freiburg, Germany in July 2011 to discuss novel insights into and approaches to myeloma bone disease and other bone-seeking tumors. This review briefly summarizes the most prominent data of the meeting and current literature on our understanding of bone disease, the role of imaging techniques, operative interventions and systemic bone-seeking treatment, all of which should further improve our future therapeutic choices.

  18. Organic Dust, Lipopolysaccharide, and Peptidoglycan Inhalant Exposures Result in Bone Loss/Disease

    PubMed Central

    Dusad, Anand; Thiele, Geoff M.; Klassen, Lynell W.; Gleason, Angela M.; Bauer, Christopher; Mikuls, Ted R.; Duryee, Michael J.; West, William W.; Romberger, Debra J.

    2013-01-01

    Skeletal health consequences associated with chronic inflammatory respiratory disease, and particularly chronic obstructive pulmonary disease (COPD), contribute to overall disease morbidity. Agricultural environmental exposures induce significant airway diseases, including COPD. However, animal models to understand inhalant exposure–induced lung injury and bone disease have not been described. Using micro–computed tomography (micro-CT) imaging technology and histology, bone quantity and quality measurements were investigated in mice after repetitive intranasal inhalation exposures to complex organic dust extracts (ODEs) from swine confinement facilities. Comparison experiments with LPS and peptidoglycan (PGN) alone were also performed. After 3 weeks of repetitive ODE inhalation exposure, significant loss of bone mineral density and trabecular bone volume fraction was evident, with altered morphological microarchitecture changes in the trabecular bone, compared with saline-treated control animals. Torsional resistance was also significantly reduced. Compared with saline treatment, ODE-treated mice demonstrated decreased collagen and proteoglycan content in their articular cartilage, according to histopathology. Significant bone deterioration was also evident after repetitive intranasal inhalant treatment with LPS and PGN. These findings were not secondary to animal distress, and not entirely dependent on the degree of induced lung parenchymal inflammation. Repetitive LPS treatment demonstrated the most pronounced changes in bone parameters, and PGN treatment resulted in the greatest lung parenchymal inflammatory changes. Collectively, repetitive inhalation exposures to noninfectious inflammatory agents such as complex organic dust, LPS, and PGN resulted in bone loss. This animal model may contribute to efforts toward understanding the mechanisms and evaluating the therapeutics associated with adverse skeletal health consequences after subchronic airway injury

  19. Role of Nanoparticles in Drug Delivery and Regenerative Therapy for Bone Diseases.

    PubMed

    Gera, Sonia; Sampathi, Sunitha; Dodoala, Sujatha

    2016-12-30

    Osteoporosis (OP) is a disease characterized by progressive bone loss due to aging and menopause in women leading to bone fragility with increased susceptibility towards fractures. The silent disease weakens the bone by altering its microstructure and mass. Therapy is based on either promoting strength (via osteoblast action) or preventing disease (via osteoclast action). Current therapy with different drugs belonging to antiresorptive, anabolic and hormonal classification suffers from poor pharmacokinetic and pharmacodynamic profile. Therapeutics and diagnostics for bone tissue have always been a hard task and presents a great challenge. Nanoparticles (NPs) provide breakthrough as an alternative therapeutic carrier and biomedical imaging tool in bone diseases. Nanotechnology advancements include the use of inorganic particles containing gold, platinum, silica and ceria with an additional advantage of osteoblastic proliferation along with other nano rewards. The current review highlights potential applications of NPs in osteoporosis with prime focus on the use of organic and inorganic particles for drug delivery, biomedical imaging as well as regenerative therapy. Incorporation of NPs into the scaffolds is a more recent technique for improving mechanical strength as well as regeneration during bone grafting. Targeted, modified and coated magnetic nanoparticles along with gold and quantum dots provide golden opportunities for biomedical imaging by replacing the traditional invasive radionuclide techniques.

  20. [Current approaches in multiple myeloma and other cancer-related bone diseases].

    PubMed

    Engelhardt, M; Kleber, M; Udi, J; Wäsch, R

    2012-05-01

    Multiple myeloma (MM) ranges second of all hematological malignancies and occurs most commonly in elderly patients. Almost all MM patients develop bone lesions in the course of their disease or have evidence of bone loss at initial diagnosis. Whole-body conventional radiography remains the gold standard in the diagnostic evaluation, albeit computed tomography (CT) and magnetic resonance imaging (MRI) are increasingly used as complementary techniques in the more sensitive detection of osteolytic processes. Bisphosphonates like zoledronate or pamidronate represent the cornerstone therapeutics in osteolytic disease, and are effective supportives to potent anti-myeloma therapies, including novel agents such as the proteasome inhibitor bortezomib or immunomodulatory drugs (IMIDs, e. g. thalidomide or lenalidomide). Several studies are ongoing to investigate the effects of alternative bone-seeking agents and their therapeutic potential for the management of myeloma bone disease, such as denosumab (RANKL-neutralizing antibody), anti-sclerostin (monoclonal antibody, generated against sclerostin) or sotatercept (potent activin-A inhibitor). This review summarizes the most prominent data on myeloma bone disease pathogenesis, the role of imaging techniques as well as therapy and prevention of lytic complications in myeloma which may similarly or equally be true for other bone metastases-inducing solid tumors.

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

    PubMed

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

    2012-08-01

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

  2. Autologous bone marrow stromal cells are promising candidates for cell therapy approaches to treat bone degeneration in sickle cell disease.

    PubMed

    Lebouvier, Angélique; Poignard, Alexandre; Coquelin-Salsac, Laura; Léotot, Julie; Homma, Yasuhiro; Jullien, Nicolas; Bierling, Philippe; Galactéros, Frédéric; Hernigou, Philippe; Chevallier, Nathalie; Rouard, Hélène

    2015-11-01

    Osteonecrosis of the femoral head is a frequent complication in adult patients with sickle cell disease (SCD). To delay hip arthroplasty, core decompression combined with concentrated total bone marrow (BM) treatment is currently performed in the early stages of the osteonecrosis. Cell therapy efficacy depends on the quantity of implanted BM stromal cells. For this reason, expanded bone marrow stromal cells (BMSCs, also known as bone marrow derived mesenchymal stem cells) can be used to improve osteonecrosis treatment in SCD patients. In this study, we quantitatively and qualitatively evaluated the function of BMSCs isolated from a large number of SCD patients with osteonecrosis (SCD-ON) compared with control groups (patients with osteonecrosis not related to SCD (ON) and normal donors (N)). BM total nuclear cells and colony-forming efficiency values (CFE) were significantly higher in SCD-ON patients than in age and sex-matched controls. The BMSCs from SCD-ON patients were similar to BMSCs from the control groups in terms of their phenotypic and functional properties. SCD-ON patients have a higher frequency of BMSCs that retain their bone regeneration potential. Our findings suggest that BMSCs isolated from SCD-ON patients can be used clinically in cell therapy approaches. This work provides important preclinical data that is necessary for the clinical application of expanded BMSCs in advanced therapies and medical products.

  3. 3D image analysis and artificial intelligence for bone disease classification.

    PubMed

    Akgundogdu, Abdurrahim; Jennane, Rachid; Aufort, Gabriel; Benhamou, Claude Laurent; Ucan, Osman Nuri

    2010-10-01

    In order to prevent bone fractures due to disease and ageing of the population, and to detect problems while still in their early stages, 3D bone micro architecture needs to be investigated and characterized. Here, we have developed various image processing and simulation techniques to investigate bone micro architecture and its mechanical stiffness. We have evaluated morphological, topological and mechanical bone features using artificial intelligence methods. A clinical study is carried out on two populations of arthritic and osteoporotic bone samples. The performances of Adaptive Neuro Fuzzy Inference System (ANFIS), Support Vector Machines (SVM) and Genetic Algorithm (GA) in classifying the different samples have been compared. Results show that the best separation success (100 %) is achieved with Genetic Algorithm.

  4. Prevalence of Paget's disease of bone in hospital patients in Jerusalem: an epidemiologic study.

    PubMed

    Bloom, R A; Libson, E; Blank, P; Nubani, N

    1985-12-01

    Epidemiological studies have revealed the widely varied prevalence of Paget's disease of bone. The highest rates have been found in parts of England. The disease has been reported only infrequently in Jews and no previous studies of prevalence have been performed in the Middle East or Asia. In the present study an age- and sex-standardized rate of 1% was found among Jews, which is similar to that in many southern European populations. No case of Paget's disease of bone was found among Arabs in this study.

  5. The Nature of Expansion of Paget’s Disease of Bone

    DTIC Science & Technology

    2013-04-01

    differentiation: Increased levels of CCL20 are expressed in subchondral bone tissue of rheumatoid arthritis patients. J Cell Physiol. 2007;210(3):798-806...osteoporosis (13, 14). Yet despite the frequency of the disease, the etiology of the disease remains elusive and highly controversial. We have been able

  6. [Genomic study of susceptibility genes for common bone and joint diseases].

    PubMed

    Ikegawa, Shiro

    2009-06-01

    Common bone and joint diseases like osteoarthritis and lumbar disc disease are polygenic diseases caused by genetic and environment factors. We are challenging susceptibility genes for common bone and joint diseases using association study as a tool. By a combination of candidate-gene approach and whole-genome screen, we have succeeded in identification of five genes for osteoarthritis and for lumbar disc diseases, respectively. In the present paper, I mention the main genes among them, ASPN, GDF5 and DVWA for osteoarthritis, and TBSP2 and MMP9 for lumbar disc disease. Identification of the new genes will open a new window for the clarification of pathomechanism of the diseases and their treatment.

  7. Reactive oxygen species and oxidative stress in osteoclastogenesis, skeletal aging and bone diseases.

    PubMed

    Callaway, Danielle A; Jiang, Jean X

    2015-07-01

    Osteoclasts are cells derived from bone marrow macrophages and are important in regulating bone resorption during bone homeostasis. Understanding what drives osteoclast differentiation and activity is important when studying diseases characterized by heightened bone resorption relative to formation, such as osteoporosis. In the last decade, studies have indicated that reactive oxygen species (ROS), including superoxide and hydrogen peroxide, are crucial components that regulate the differentiation process of osteoclasts. However, there are still many unanswered questions that remain. This review will examine the mechanisms by which ROS can be produced in osteoclasts as well as how it may affect osteoclast differentiation and activity through its actions on osteoclastogenesis signaling pathways. In addition, the contribution of ROS to the aging-associated disease of osteoporosis will be addressed and how targeting ROS may lead to the development of novel therapeutic treatment options.

  8. Calcium Regulation and Bone Mineral Metabolism in Elderly Patients with Chronic Kidney Disease

    PubMed Central

    Tejwani, Vickram; Qian, Qi

    2013-01-01

    The elderly chronic kidney disease (CKD) population is growing. Both aging and CKD can disrupt calcium (Ca2+) homeostasis and cause alterations of multiple Ca2+-regulatory mechanisms, including parathyroid hormone, vitamin D, fibroblast growth factor-23/Klotho, calcium-sensing receptor and Ca2+-phosphate product. These alterations can be deleterious to bone mineral metabolism and soft tissue health, leading to metabolic bone disease and vascular calcification and aging, termed CKD-mineral and bone disorder (MBD). CKD-MBD is associated with morbid clinical outcomes, including fracture, cardiovascular events and all-cause mortality. In this paper, we comprehensively review Ca2+ regulation and bone mineral metabolism, with a special emphasis on elderly CKD patients. We also present the current treatment-guidelines and management options for CKD-MBD. PMID:23760058

  9. Vascularised bone graft and osteotomy of the radius in Kienböck's disease.

    PubMed

    Zafra, Manuel; Carrasco-Becerra, Carmen; Carpintero, Pedro

    2005-04-01

    Treatment of stage IIIA and III B avascular necrosis of the lunate bone remains controversial. We present a series of 5 cases in young patients treated with a vascularised bone graft from the second metacarpal, combined with a lateral shortening and closing wedge osteotomy of the radius. Good clinical and radiographic results were obtained and disease progression was halted with the combination of these two surgical procedures.

  10. Effects of bioactive fatty acid amide derivatives in zebrafish scale model of bone metabolism and disease.

    PubMed

    Carnovali, M; Ottria, R; Pasqualetti, S; Banfi, G; Ciuffreda, P; Mariotti, M

    2016-02-01

    The endocannabinoid system (which includes fatty acid derivatives, receptors, and metabolizing enzymes) is involved in a variety of physiological processes, including bone metabolism in which it regulates the function of osteoblasts and osteoclasts, as well as differentiation of their precursors. The zebrafish (Danio rerio) provides a useful animal model for bone research since zebrafish bones develop rapidly and are anatomically similar to mammalian bones. Putative orthologues and paralogs of endocannabinoid genes have recently been identified in zebrafish, demonstrating the presence of cannabinoid type 1 (CB1) and type 2 (CB2) receptors with affinity to endocannabinoid ligands. To identify therapeutic molecules potentially useful in bone-related diseases, we evaluated the in vivo effects of exposure to long-chain fatty acid amides in adult zebrafish. Using a well-established zebrafish scale model, we found that anandamide and N-linoleoylethanolamine are able to stimulate bone formation by increasing alkaline phosphatase activity in physiological conditions. In addition, they prevent the alteration of bone markers in a prednisolone-induced osteoporosis model in adult zebrafish scales, whereas their esterified forms do not. These data suggest that long-chain fatty acid amides are involved in regulating bone metabolism in zebrafish scales and that the CB2 receptor is a key mediator in this process.

  11. Klotho preservation via histone deacetylase inhibition attenuates chronic kidney disease-associated bone injury in mice

    PubMed Central

    Lin, Wenjun; Li, Yanning; chen, Fang; Yin, Shasha; Liu, Zhihong; Cao, Wangsen

    2017-01-01

    Bone loss and increased fracture are the devastating outcomes of chronic kidney disease-mineral and bone disorder (CKD-MBD) resulting from Klotho deficit-related mineral disturbance and hyperparathyroidism. Because Klotho down-regulation after renal injury is presumably affected by aberrant histone deacetylase (HDAC) activities, here we assess whether HDAC inhibition prevents Klotho loss and attenuates the CKD-associated bone complication in a mouse model of CKD-MBD. Mice fed adenine-containing diet developed the expected renal damage, a substantial Klotho loss and the deregulated key factors causally affecting bone remodeling, which were accompanied by a marked reduction of bone mineral density. Intriguingly, administration of a potent HDAC inhibitor trichostatin A (TSA) impressively alleviated the Klotho deficit and the observed alterations of serum, kidney and bone. TSA prevented Klotho loss by increasing the promoter-associated histone acetylation, therefore increasing Klotho transcription. More importantly the mice lacking Klotho by siRNA interference largely abolished the TSA protections against the serum and renal abnormalities, and the deranged bone micro-architectures. Thus, our study identified Klotho loss as a key event linking HDAC deregulation to the renal and bone injuries in CKD-MBD mice and demonstrated the therapeutic potentials of endogenous Klotho restoration by HDAC inhibition in treating CKD and the associated extrarenal complications. PMID:28387374

  12. The role of bone in CKD-mediated mineral and vascular disease.

    PubMed

    Khouzam, Nadine M; Wesseling-Perry, Katherine; Salusky, Isidro B

    2015-09-01

    Cardiovascular disease is the leading cause of death in pediatric patients with chronic kidney disease (CKD), and vascular calcifications start early in the course of CKD. Based on the growing body of evidence that alterations of bone and mineral metabolism and the therapies designed to treat the skeletal consequences of CKD are linked to cardiovascular calcifications, the Kidney Disease, Improving Global Outcomes (KDIGO) working group redefined renal osteodystrophy as a systemic disorder of mineral and bone metabolism due to CKD, and this newly defined disorder is now known as "chronic kidney disease-mineral bone disorder (CKD-MBD)". Elevated fibroblast growth factor 23 (FGF23), a bone-derived protein, is the first biochemical abnormality to be associated with CKD-MBD, and high FGF23 levels correlate with increased cardiovascular morbidity and mortality, suggesting that bone is central to both initiating and perpetuating the abnormal mineral metabolism and vascular disease in CKD. The current standard therapies for CKD-MBD affect FGF23 levels differently; non-calcium-based binders with or without concurrent use of dietary phosphate restriction reduce FGF23 levels, while calcium-based binders seem to either increase or have no effect on FGF23 levels. Active vitamin D sterols increase FGF23 levels, whereas therapy with calcimimetics decreases FGF23 levels. Thus, the appropriate therapy that will minimize the rise in FGF23 and prevent cardiovascular morbidity remains to be defined.

  13. The impact of methods for estimating bone health and the global burden of bone disease.

    PubMed

    Cole, Zoë A; Dennison, Elaine M; Cooper, Cyrus

    2009-01-01

    Osteoporosis constitutes a major public health problem through its association with age related fractures. Fracture rates are generally higher in caucasian women than in other populations. Important determinants include estrogen deficiency in women, low body mass index, cigarette smoking, alcohol consumption, poor dietary calcium intake, physical inactivity, certain drugs and illnesses. Thus, modification of physical activity and dietary calcium/vitamin D nutrition should complement high risk approaches. In addition, the recently developed WHO algorithm for evaluation of 10-year absolute risk of fracture provides a means whereby various therapies can be targeted cost-effectively to those at risk. Risk factors, together with bone mineral density (BMD) and biochemical indices of bone turnover, can be utilised to derive absolute risks of fracture and cost-utility thresholds at which treatment is justified. These data will provide the basis for translation into coherent public health strategies aiming to prevent osteoporosis both in individuals and in the general population.

  14. SRC kinase inhibition with saracatinib limits the development of osteolytic bone disease in multiple myeloma

    PubMed Central

    Binsfeld, Marilène; Marty, Caroline; Plougonven, Erwan; Dubois, Sophie; Mahli, Nadia; Moermans, Karen; Carmeliet, Geert; Léonard, Angélique; Baron, Frédéric; Beguin, Yves; Menu, Eline; Cohen-Solal, Martine; Caers, Jo

    2016-01-01

    Multiple myeloma (MM)-associated osteolytic bone disease is a major cause of morbidity and mortality in MM patients and the development of new therapeutic strategies is of great interest. The proto-oncogene SRC is an attractive target for such a strategy. In the current study, we investigated the effect of treatment with the SRC inhibitor saracatinib (AZD0530) on osteoclast and osteoblast differentiation and function, and on the development of MM and its associated bone disease in the 5TGM.1 and 5T2MM murine MM models. In vitro data showed an inhibitory effect of saracatinib on osteoclast differentiation, polarization and resorptive function. In osteoblasts, collagen deposition and matrix mineralization were affected by saracatinib. MM cell proliferation and tumor burden remained unaltered following saracatinib treatment and we could not detect any synergistic effects with drugs that are part of standard care in MM. We observed a marked reduction of bone loss after treatment of MM-bearing mice with saracatinib as reflected by a restoration of trabecular bone parameters to levels observed in naive control mice. Histomorphometric analyses support that this occurs through an inhibition of bone resorption. In conclusion, these data further establish SRC inhibition as a promising therapeutic approach for the treatment of MM-associated osteolytic bone disease. PMID:27095574

  15. Bone mass and vitamin D levels in Parkinson's disease: is there any difference between genders?

    PubMed

    Ozturk, Erhan Arif; Gundogdu, Ibrahim; Tonuk, Burak; Kocer, Bilge Gonenli; Tombak, Yasemin; Comoglu, Selcuk; Cakci, Aytul

    2016-08-01

    [Purpose] The aim of this study was to determine the bone mineral density, vitamin D level, and frequencies of osteopenia and osteoporosis in patients with Parkinson's disease and to compare male and female patients with the controls separately. [Subjects and Methods] One hundred fifteen Parkinson's disease patients (47 males, 68 females; age range: 55-85 years) and 117 age- and gender-matched controls (47 males, 70 females) were enrolled in the study. Bone mineral density measured by dual-energy X-ray absorptiometry and serum D vitamin levels of each participant were recorded. [Results] The mean lumbar spine, femur neck, and total femur bone mineral density levels, T-scores, and vitamin D levels were found to be significantly lower in Parkinson's disease patients in both genders. Furthermore, osteoporosis rates were found be significantly higher only in female Parkinson's disease patients compared with female controls. [Conclusion] Data from the present study revealed that while osteoporosis was significantly higher only in female Parkinson's disease patients, all Parkinson's disease patients had lower bone mineral density scores and vitamin D levels compared with the controls regardless of gender, suggesting that clinicians should pay attention to the osteoporosis risk in Parkinson's disease and that adequate preventive measures should be taken in order to limit the future risk due to osteoporotic fractures.

  16. Bone Morphogenetic Protein (BMP) signaling in development and human diseases

    PubMed Central

    Wang, Richard N.; Green, Jordan; Wang, Zhongliang; Deng, Youlin; Qiao, Min; Peabody, Michael; Zhang, Qian; Ye, Jixing; Yan, Zhengjian; Denduluri, Sahitya; Idowu, Olumuyiwa; Li, Melissa; Shen, Christine; Hu, Alan; Haydon, Rex C.; Kang, Richard; Mok, James; Lee, Michael J.; Luu, Hue L.; Shi, Lewis L.

    2014-01-01

    Bone Morphogenetic Proteins (BMPs) are a group of signaling molecules that belongs to the Transforming Growth Factor-β (TGF-β) superfamily of proteins. Initially discovered for their ability to induce bone formation, BMPs are now known to play crucial roles in all organ systems. BMPs are important in embryogenesis and development, and also in maintenance of adult tissue homeostasis. Mouse knockout models of various components of the BMP signaling pathway result in embryonic lethality or marked defects, highlighting the essential functions of BMPs. In this review, we first outline the basic aspects of BMP signaling and then focus on genetically manipulated mouse knockout models that have helped elucidate the role of BMPs in development. A significant portion of this review is devoted to the prominent human pathologies associated with dysregulated BMP signaling. PMID:25401122

  17. Paget disease of the bone: does it exist in Saudi Arabia?

    PubMed

    Alshaikh, Omalkhaire M; Almanea, Hadeel; Alzahrani, Ali S

    2011-01-01

    Paget disease of the bone is a chronic disease characterized by accelerated bone turnover with abnormal repair leading to expansion, pain and deformities. The disease is common in the West, but little if any information is available on its existence in the Arab world, including Saudi Arabia. We present four cases of Saudi patients with Paget disease with variable presentations. The first case, a 63-year-old woman with a history of papillary thyroid cancer, presented with bone, shoulder and chest wall pain and foci of uptake in the ribs and skull that were thought to be metastases, indicating the possibility of diagnostic difficulty in a patient with history of malignancy. Bone biopsy confirmed the diagnosis of Paget disease. The second case was a 47-year-old asymptomatic woman with an elevated alkaline phosphatase of 427 U/L, a common presentation but at an unusual age. Plain x-rays and bone scan confirmed the diagnosis. The third case was a 43-year-old man who presented with hearing impairment and right knee osteoarthritis, unusual presentations at a young age leading to a delay in diagnosis. The fourth case was a 45-year-old man who presented with sacroiliac pain and normal biochemical values, including a normal alkaline phosphatase. Bone biopsy unexpectedly revealed features of Paget disease, which evolved over time into a classical form. A common feature in all except the first case was the relatively young age. Paget disease does exist in Saudi Arabia, and it should be considered in the differential diagnosis of similar cases.

  18. [Analysis of Musculoskeletal Systems and Their Diseases. Integrated treatments for osteoporosis toward harmony of bone and muscle].

    PubMed

    Kanazawa, Ippei; Sugimoto, Toshitsugu

    2015-08-01

    Osteoporosis and sarcopenia directly affect healthy life expectancy in elderly people ; therefore, both diseases become social problem around the world. Sarcopenia increases the risk of osteoporotic fracture. Thus, not only agents affecting bone tissue directly but also treatments for sarcopenia are important for management of osteoporosis. Recently, it has been shown that there is an interaction between bone and muscle. Several hormones affect muscle and bone simultaneously. Moreover, myokines secreted from muscle are reported to regulate bone metabolism. On the other hand, several systemic and local factors derived from bone also affect muscle tissue. Therefore, further studies are necessary to develop the integrated treatments for osteoporosis toward harmony of bone and muscle.

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

    NASA Technical Reports Server (NTRS)

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

    2003-01-01

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

  20. Cilia/Ift protein and motor-related bone diseases and mouse models

    PubMed Central

    Yuan, Xue; Yang, Shuying

    2015-01-01

    Primary cilia are essential cellular organelles projecting from the cell surface to sense and transduce developmental signaling. They are tiny but have complicated structures containing microtubule (MT)-based internal structures (the axoneme) and mother centriole formed basal body. Intraflagellar transport (Ift) operated by Ift proteins and motors are indispensable for cilia formation and function. Mutations in Ift proteins or Ift motors cause various human diseases, some of which have severe bone defects. Over the last few decades, major advances have occurred in understanding the roles of these proteins and cilia in bone development and remodeling by examining cilia/Ift protein-related human diseases and establishing mouse transgenic models. In this review, we describe current advances in the understanding of the cilia/Ift structure and function. We further summarize cilia/Ift-related human diseases and current mouse models with an emphasis on bone-related phenotypes, cilia morphology, and signaling pathways. PMID:25553465

  1. Cilia/Ift protein and motor -related bone diseases and mouse models.

    PubMed

    Yuan, Xue; Yang, Shuying

    2015-01-01

    Primary cilia are essential cellular organelles projecting from the cell surface to sense and transduce developmental signaling. They are tiny but have complicated structures containing microtubule (MT)-based internal structures (the axoneme) and mother centriole formed basal body. Intraflagellar transport (Ift) operated by Ift proteins and motors are indispensable for cilia formation and function. Mutations in Ift proteins or Ift motors cause various human diseases, some of which have severe bone defects. Over the last few decades, major advances have occurred in understanding the roles of these proteins and cilia in bone development and remodeling by examining cilia/Ift protein-related human diseases and establishing mouse transgenic models. In this review, we describe current advances in the understanding of the cilia/Ift structure and function. We further summarize cilia/Ift-related human diseases and current mouse models with an emphasis on bone-related phenotypes, cilia morphology, and signaling pathways.

  2. Therapeutic application of mesenchymal stem cells in bone and joint diseases.

    PubMed

    Liu, Yi; Wu, Jianmei; Zhu, Youming; Han, Jinxiang

    2014-02-01

    Mesenchymal stem cells (MSCs), the non-hematopoietic progenitor cells, are multi-potent stem cells from a variety of tissues with the capability of self-renewal, proliferation, differentiation into multi-lineage cell types, as well as anti-inflammatory and immunomodulatory. These properties make MSCs an ideal source of cell therapy in bone and joint diseases. This review describes the advances of animal study and preliminary clinical application in the past few years, related to MSC-based cell therapy in the common bone and joint diseases, including osteoarthritis, rheumatoid arthritis, osteoporosis, osteonecrosis of the femoral head and osteogenesis imperfecta. It highlights the promising prospect of MSC in clinical application of bone and joint diseases.

  3. Nutritional and metabolic correlates of cardiovascular and bone disease in HIV-infected patients.

    PubMed

    Fitch, Kathleen; Grinspoon, Steven

    2011-12-01

    The treatment of HIV infection has dramatically reduced the incidence of AIDS-related illnesses. At the same time, non-AIDS-related illnesses such as cardiovascular and bone disease are becoming more prevalent in this population. The mechanisms of these illnesses are complex and are related in part to the HIV virus, antiretroviral medications prescribed for HIV infection, traditional risk factors exacerbated by HIV, and lifestyle and nutritional factors. Further prospective research is needed to clarify the mechanisms by which HIV, antiretroviral medications, and nutritional abnormalities contribute to bone and cardiovascular disease in the HIV population. Increasingly, it is being recognized that optimizing the treatment of HIV infection to improve immune function and reduce viral load may also benefit the development of non-AIDS-related illnesses such as cardiovascular and bone disease.

  4. Polyacrylamide gel disc electrophoresis of alkaline phosphatase isoenzymes in bone and liver disease.

    PubMed Central

    Warnes, T W; Hine, P; Kay, G

    1976-01-01

    Acrylamide gel disc electrophoresis provides a reliable and reasonably rapid method of differentiating the raised serum alkaline phosphatase (AP) of bone origin from that of liver origin. The technique has been placed for the first time on a semiquantitative basis. Measurement of both band width and band position effectively distinguishes the bone from the liver isoenzyme, but band width provides superior discrimination. An origin band was seen in none of the normal subjects and in only 7% of patients with bone disease but was present in 78% of patients with liver disease, a highly significant increase. Fifty percent of normal individuals had a small-intestinal band in serum taken two hours after a meal, as did 35% of patients with liver disease, but the incidence of intestinal bands in bone disease was only 11%, significantly less than in the other two groups. The genetic control of small-intestinal AP in serum has been confirmed, but it has been demonstrated that the decrease of intestinal AP in bone disorders is not genetically determined. Images PMID:977779

  5. Osteoporosis: Modern Paradigms for Last Century's Bones.

    PubMed

    Kruger, Marlena C; Wolber, Frances M

    2016-06-17

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

  6. Biosilica-based strategies for treatment of osteoporosis and other bone diseases.

    PubMed

    Schröder, Heinz C; Wiens, Matthias; Wang, Xiaohong; Schloßmacher, Ute; Müller, Werner E G

    2011-01-01

    Osteoporosis is a common disease in later life, which has become a growing public health problem. This degenerative bone disease primarily affects postmenopausal women, but also men may suffer from reduced bone mineral density. The development of prophylactic treatments and medications of osteoporosis has become an urgent issue due to the increasing proportion of the elderly in the population. Apart from medical/hormonal treatments, current strategies for prophylaxis of osteoporosis are primarily based on calcium supplementation as a main constituent of bone hydroxyapatite mineral. Despite previous reports suggesting an essential role in skeletal growth and development, the significance of the trace element silicon in human bone formation has attracted major scientific interest only rather recently. The interest in silicon has been further increased by the latest discoveries in the field of biosilicification, the formation of the inorganic silica skeleton of the oldest still extant animals on Earth, the sponges, which revealed new insights in the biological function of this element. Sponges make use of silicon to build up their inorganic skeleton which consists of biogenously formed polymeric silica (biosilica). The formation of biosilica is mediated by specific enzymes, silicateins, which have been isolated, characterized, and expressed in a recombinant way. Epidemiological studies revealed that dietary silicon reduces the risk of osteoporosis and other bone diseases. Recent results allowed for the first time to understand the molecular mechanism underlying the protective effect of silicic acid/biosilica against osteoporosis. Biosilica was shown to modulate the ratio of expression of two cytokines involved in bone formation-RANKL and osteoprotegerin. Hence, biosilica has been proposed to have a potential in prophylaxis and therapy of osteoporosis and related bone diseases.

  7. Clinical and Genetic Advances in Paget's Disease of Bone: a Review.

    PubMed

    Alonso, N; Calero-Paniagua, I; Del Pino-Montes, J

    2017-01-01

    Paget's disease of bone (PDB) is the second most common metabolic bone disorder, after osteoporosis. It is characterised by focal areas of increased and disorganised bone turnover, coupled with increased bone formation. This disease usually appears in the late stages of life, being slightly more frequent in men than in women. It has been reported worldwide, but primarily affects individuals of British descent. Majority of PDB patients are asymptomatic, but clinical manifestations include pain, bone deformity and complications, like pathological fractures and deafness. The causes of the disease are poorly understood and it is considered as a complex trait, combining genetic predisposition with environmental factors. Linkage analysis identified SQSTM1, at chromosome 5q35, as directly related to the disease. A number of mutations in this gene have been reported, pP392L being the most common variant among different populations. Most of these variants affect the ubiquitin-associated (UBA) domain of the protein, which is involved in autophagy processes. Genome-wide association studies enlarged the number of loci associated with PDB, and further fine-mapping studies, combined with functional analysis, identified OPTN and RIN3 as causal genes for Paget's disease. A combination of risk alleles identified by genome-wide association studies led to the development of a score to predict disease severity, which could improve the management of the disease. Further studies need to be conducted to elucidate other important aspects of the trait, such as its focal nature and the epidemiological changes found in some populations. In this review, we summarize the clinical characteristics of the disease and the latest genetic advances to identify susceptibility genes. We also list current available treatments and prospective options.

  8. Computational brittle fracture using smooth particle hydrodynamics

    SciTech Connect

    Mandell, D.A.; Wingate, C.A.; Schwalbe, L.A.

    1996-10-01

    We are developing statistically based, brittle-fracture models and are implementing them into hydrocodes that can be used for designing systems with components of ceramics, glass, and/or other brittle materials. Because of the advantages it has simulating fracture, we are working primarily with the smooth particle hydrodynamics code SPBM. We describe a new brittle fracture model that we have implemented into SPBM. To illustrate the code`s current capability, we have simulated a number of experiments. We discuss three of these simulations in this paper. The first experiment consists of a brittle steel sphere impacting a plate. The experimental sphere fragment patterns are compared to the calculations. The second experiment is a steel flyer plate in which the recovered steel target crack patterns are compared to the calculated crack patterns. We also briefly describe a simulation of a tungsten rod impacting a heavily confined alumina target, which has been recently reported on in detail.

  9. The bone marrow microenvironment as a sanctuary for minimal residual disease in CML

    PubMed Central

    Nair, Rajesh R.; Tolentino, Joel; Hazlehurst, Lori A.

    2012-01-01

    Bcr-abl kinase inhibitors have provided proof of principal that targeted therapy holds great promise for the treatment of cancer. However, despite the success of these agents in treating chronic myelogenous leukemia (CML), the majority of patients continue to present with minimal residual disease contained within the bone marrow microenvironment. These clinical observations suggest that the bone marrow microenvironment may provide survival signals that contribute to the failure to eliminate minimal residual disease. The bone marrow microenvironment is comprised of multiple sub-domains which vary in cellular composition and gradients of soluble factors and matrix composition. Experimental evidence indicates that exposure of tumor cells to either bone marrow derived soluble factors or matrixes can confer a multi-drug resistance phenotype. Together, these data indicate that targeting such pathways may be a viable approach for increasing the efficacy of chemotherapy. Moreover, we propose that personalized medicine must go beyond understanding predictive models inherent to tumors but rather build predictive models that consider diversity in response due to interactions with the tumor microenvironment. This review will focus on CML, however, understanding the contribution of the bone marrow microenvironment could contribute to rationale combination therapy in other types of leukemia, multiple myeloma and solid tumors which metastasize to the bone. PMID:20382130

  10. Wnt signaling in bone formation and its therapeutic potential for bone diseases

    PubMed Central

    Kim, Jeong Hwan; Liu, Xing; Wang, Jinhua; Chen, Xiang; Zhang, Hongyu; Kim, Stephanie H.; Cui, Jing; Li, Ruidong; Zhang, Wenwen; Kong, Yuhan; Zhang, Jiye; Shui, Wei; Lamplot, Joseph; Rogers, Mary Rose; Zhao, Chen; Wang, Ning; Rajan, Prashant; Tomal, Justin; Statz, Joseph; Wu, Ningning; Luu, Hue H.; Haydon, Rex C.

    2013-01-01

    The Wnt signaling pathway plays an important role not only in embryonic development but also in the maintenance and differentiation of the stem cells in adulthood. In particular, Wnt signaling has been shown as an important regulatory pathway in the osteogenic differentiation of mesenchymal stem cells. Induction of the Wnt signaling pathway promotes bone formation while inactivation of the pathway leads to osteopenic states. Our current understanding of Wnt signaling in osteogenesis elucidates the molecular mechanisms of classic osteogenic pathologies. Activating and inactivating aberrations of the canonical Wnt signaling pathway in osteogenesis results in sclerosteosis and osteoporosis respectively. Recent studies have sought to target the Wnt signaling pathway to treat osteogenic disorders. Potential therapeutic approaches attempt to stimulate the Wnt signaling pathway by upregulating the intracellular mediators of the Wnt signaling cascade and inhibiting the endogenous antagonists of the pathway. Antibodies against endogenous antagonists, such as sclerostin and dickkopf-1, have demonstrated promising results in promoting bone formation and fracture healing. Lithium, an inhibitor of glycogen synthase kinase 3β, has also been reported to stimulate osteogenesis by stabilizing β catenin. Although manipulating the Wnt signaling pathway has abundant therapeutic potential, it requires cautious approach due to risks of tumorigenesis. The present review discusses the role of the Wnt signaling pathway in osteogenesis and examines its targeted therapeutic potential. PMID:23514963

  11. 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

  12. 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.

  13. Bone Mass and Mineral Metabolism Alterations in Adult Celiac Disease: Pathophysiology and Clinical Approach

    PubMed Central

    Di Stefano, Michele; Mengoli, Caterina; Bergonzi, Manuela; Corazza, Gino Roberto

    2013-01-01

    Osteoporosis affects many patients with celiac disease (CD), representing the consequence of calcium malabsorption and persistent activation of mucosal inflammation. A slight increase of fracture risk is evident in this condition, particularly in those with overt malabsorption and in postmenopausal state. The adoption of a correct gluten-free diet (GFD) improves bone derangement, but is not able to normalize bone mass in all the patients. Biomarkers effective in the prediction of bone response to gluten-free diet are not yet available and the indications of guidelines are still imperfect and debated. In this review, the pathophysiology of bone loss is correlated to clinical aspects, defining an alternative proposal of management for this condition. PMID:24284619

  14. Brittleness Effect on Rock Fatigue Damage Evolution

    NASA Astrophysics Data System (ADS)

    Nejati, Hamid Reza; Ghazvinian, Abdolhadi

    2014-09-01

    The damage evolution mechanism of rocks is one of the most important aspects in studying of rock fatigue behavior. Fatigue damage evolution of three rock types (onyx marble, sandstone and soft limestone) with different brittleness were considered in the present study. Intensive experimental tests were conducted on the chosen rock samples and acoustic emission (AE) sensors were used in some of them to monitor the fracturing process. Experimental tests indicated that brittleness strongly influences damage evolution of rocks in the course of static and dynamic loading. AE monitoring revealed that micro-crack density induced by the applied loads during different stages of the failure processes increases as rock brittleness increases. Also, results of fatigue tests on the three rock types indicated that the rock with the most induced micro-cracks during loading cycles has the least fatigue life. Furthermore, the condition of failure surfaces of the studied rocks samples, subjected to dynamic and static loading, were evaluated and it was concluded that the roughness of failure surfaces is influenced by loading types and rock brittleness. Dynamic failure surfaces were rougher than static ones and low brittle rock demonstrate a smoother failure surface compared to high brittle rock.

  15. Periodontal disease exacerbates systemic ovariectomy-induced bone loss in mice.

    PubMed

    Anbinder, Ana Lia; Moraes, Renata M; Lima, Gabriela M G; Oliveira, Felipe E; Campos, Débora R C; Rossoni, Rodnei D; Oliveira, Luciane D; Junqueira, Juliana C; Ma, Yun; Elefteriou, Florent

    2016-02-01

    Periodontal pathogens and/or inflammatory products from periodontitis participate in the development or progression of systemic diseases. In this context, periodontitis acts as a modifying factor to systemic health, including diabetes and cardiovascular diseases. Osteoporosis is an increasingly prevalent condition in our aging population and considered a risk factor for periodontal disease, but the effect of periodontitis on systemic bone homeostasis is unknown. We thus evaluated the effects of experimental periodontitis (EP) on systemic bone loss and the influence of estrogen deficiency in this context, using a mouse model of combined periodontitis and osteoporosis. Experimental periodontitis (EP) was induced by a ligature insertion around the mandibular first molars and Porphyromonas gingivalis infection. Three-dimensional microcomputed tomographic analyses performed 48days following infection revealed that EP and ovariectomy (OVX) induced a significantly higher femoral and mandibular bone loss compared to EP or OVX alone. EP alone did not induce systemic bone loss. In addition, the EP+OVX and EP groups showed significantly higher levels of tumor necrosis factor (TNF)-α than OVX and control groups at end point. These results suggest that periodontitis could be a risk factor for systemic bone loss, especially in post-menopausal women, and warrant further clinical investigations to confirm this association and propose adapted prophylactic and curative therapies.

  16. Long-term bone health in glucocorticoid-treated children with rheumatic diseases.

    PubMed

    Rousseau-Nepton, Isabelle; Lang, Bianca; Rodd, Celia

    2013-03-01

    Glucocorticoids (GC) are a standard treatment for pediatric rheumatic disease. Recent literature highlights skeletal vulnerability in children with rheumatic illness, including vertebral and peripheral fractures and reductions in bone mineral density in longitudinal follow-up. Annual vertebral fracture incidence of 4-6 % in those recently diagnosed and prevalence of 7-28 % in those several years post diagnosis have been reported. The fractures are often asymptomatic, often thoracic in location, and usually of mild, anterior wedge morphology. Diseases with more systemic involvement and severe inflammation (SLE, JDM) seem to be at higher risk. Neither BMD nor GC dose are ideal predictors for risk of fractures. These children also seem to have an increased incidence of long-bone fractures, particularly in the forearm and wrist; in the scant literature, long-bone fractures are not predictive of vertebral fractures. Bone mass accrual is typically suboptimum across time, although the use of potent steroid-sparing anti-inflammatory agents may counteract the effects of GC and active disease. Vitamin D insufficiency warrants ongoing monitoring. Additional targeted studies are justified to increase understanding of bone health risks in this population.

  17. Gorham-Stout disease presenting with dyspnea and bone pain in a 9-year-old girl.

    PubMed

    Davalos, Eric A; Gandhi, Nishant M; Barank, David; Varma, Rajeev K

    2015-01-01

    Gorham-Stout (GS) disease is a rare bone disorder of unknown etiology that is characterized by local proliferation of small vascular or lymphatic channels, resulting in progressive osteolysis and bone resorption. The diagnosis of GS disease is one of exclusion, with radiography and histopathology playing key roles. We describe a 9-year-old girl who presented to us with dyspnea and bone pain. She was found to have a cystic mass of the upper extremity, multiple cystic bone lesions, multiple fractures of different ages, and pleural effusions. We review the radiologic images that helped establish the diagnosis of GS disease.

  18. Fracturing and brittleness index analyses of shales

    NASA Astrophysics Data System (ADS)

    Barnhoorn, Auke; Primarini, Mutia; Houben, Maartje

    2016-04-01

    The formation of a fracture network in rocks has a crucial control on the flow behaviour of fluids. In addition, an existing network of fractures , influences the propagation of new fractures during e.g. hydraulic fracturing or during a seismic event. Understanding of the type and characteristics of the fracture network that will be formed during e.g. hydraulic fracturing is thus crucial to better predict the outcome of a hydraulic fracturing job. For this, knowledge of the rock properties is crucial. The brittleness index is often used as a rock property that can be used to predict the fracturing behaviour of a rock for e.g. hydraulic fracturing of shales. Various terminologies of the brittleness index (BI1, BI2 and BI3) exist based on mineralogy, elastic constants and stress-strain behaviour (Jin et al., 2014, Jarvie et al., 2007 and Holt et al., 2011). A maximum brittleness index of 1 predicts very good and efficient fracturing behaviour while a minimum brittleness index of 0 predicts a much more ductile shale behaviour. Here, we have performed systematic petrophysical, acoustic and geomechanical analyses on a set of shale samples from Whitby (UK) and we have determined the three different brittleness indices on each sample by performing all the analyses on each of the samples. We show that each of the three brittleness indices are very different for the same sample and as such it can be concluded that the brittleness index is not a good predictor of the fracturing behaviour of shales. The brittleness index based on the acoustic data (BI1) all lie around values of 0.5, while the brittleness index based on the stress strain data (BI2) give an average brittleness index around 0.75, whereas the mineralogy brittleness index (BI3) predict values below 0.2. This shows that by using different estimates of the brittleness index different decisions can be made for hydraulic fracturing. If we would rely on the mineralogy (BI3), the Whitby mudstone is not a suitable

  19. Novel bromomelatonin derivatives as potentially effective drugs to treat bone diseases.

    PubMed

    Suzuki, Nobuo; Somei, Masanori; Seki, Azusa; Reiter, Russel J; Hattori, Atsuhiko

    2008-10-01

    Several reports indicate that melatonin is involved in the regulation of bone metabolism. To examine the direct effect of melatonin on osteoclasts and osteoblasts, we developed an in vitro assay using fish scales that contain osteoclasts, osteoblasts, and bone matrix, all of which are similar to those found in mammalian membrane bone. Using the assay, we demonstrated that melatonin suppressed osteoclastic and osteoblastic activities. These findings are in agreement with the reports from in vivo studies in mice and rats. In an attempt to develop molecules that increase bone mass, novel bromomelatonin derivatives were synthesized, and the effects of these chemicals on osteoclasts and osteoblasts using the scale assay were examined. As a result, novel bromomelatonin derivatives with the ability to possibly increase bone formation were identified. In scale osteoclasts, particularly, 1-benzyl-2,4,6-tribromomelatonin had a more potent activity than melatonin. In reference to osteoblasts, this agent (10(-9)-10(-6)M) significantly activated osteoblasts. The effect of 1-benzyl-2,4,6-tribromomelatonin on bone formation was confirmed in ovariectomized rats. Thus, the oral administration of 1-benzyl-2,4,6-tribromomelatonin augmented the total bone mineral density of the femoral metaphysis of ovariectomized rats. The stress-strain index of the diaphysis in 1-benzyl-2,4,6-tribromomelatonin-treated rats significantly increased in comparison with that in ovariectomized rats. In rats fed a low-calcium diet, the total bone mineral density of the femoral metaphysis significantly increased following the oral administration of 1-benzyl-2,4,6-tribromomelatonin. These studies identified a melatonin derivative that may have potential use in the treatment of bone diseases, such as osteoporosis.

  20. Smokers with emphysema and small airway disease on computed tomography have lower bone density.

    PubMed

    Pompe, Esther; de Jong, Pim A; van Rikxoort, Eva M; Gallardo Estrella, Leticia; de Jong, Werner U; Vliegenthart, Rozemarijn; Oudkerk, Matthijs; van der Aalst, Carlijn M; van Ginneken, Bram; Lammers, Jan-Willem J; Mohamed Hoesein, Firdaus Aa

    2016-01-01

    Osteoporosis is more common in patients with COPD and in smokers. The aim of this study was to assess whether measures of emphysema and airway disease on computed tomography (CT) were associated with lower bone density or vertebral fractures in smokers with and without COPD. For this purpose, we included participants from the NELSON lung cancer screening trial. Bone density was measured as Hounsfield Units in the first lumbar vertebra, and vertebral fractures were assessed semiquantitatively. The 15th percentile method (Perc15) was used to assess emphysema, and the airway lumen perimeter (Pi10) was used for airway wall thickness. Expiratory/inspiratory-ratiomean lung density (E/I-ratioMLD) was used as a measure for air trapping and tracheal index to assess tracheal deformity. Linear regression models and logistic regression models were used to assess associations between CT biomarkers, bone density, and presence of fractures. Exactly 1,093 male participants were eligible for analysis. Lower Perc15 and higher E/I-ratioMLD were significantly associated with lower bone density (b=-1.27, P=0.02 and b=-0.37, P=0.02, respectively). Pi10 and tracheal index were not associated with bone density changes. CT-derived biomarkers were not associated with fracture prevalence. Bone density is lower with increasing extent of emphysema and small airway disease but is not associated with large airway disease and tracheal deformity. This may indicate the necessity to measure bone density early in smokers with emphysema and air trapping to prevent vertebral fractures.

  1. In silico investigations of potential anabolic treatments in multiple myeloma-induced bone disease.

    PubMed

    Wang, Yan; Lin, Bo

    2013-07-01

    No anabolic drugs are currently approved to treat multiple myeloma (MM)-induced bone disease and the anti-MM agent bortezomib exhibits the anabolic effects in the clinic. In this study, we focus on investigating potential anabolic treatments of MM-induced bone disease using our previously proposed MM-bone model, with the goal for clarifying the underlying molecular/cellular mechanisms. Firstly, a variety of virtual drug treatments are explored by the parametric study to clarify the anabolic-related molecular/cellular mechanisms. The real drug (i.e., bortezomib) treatments are further examined by developing an integrated model with bortezomib to validate the clarified anabolic-related molecular/cellular mechanisms. The simulated responses to the bortezomib treatments that are validated by the clinical data are consistent with the simulated responses to the virtual drug treatments. Our study clarifies that the anabolic effects in the treatment of MM-induced bone disease are associated with promoting the differentiation of bone marrow stromal cells (BMSC) and inhibiting the apoptosis of active osteoblasts, while promoting the differentiation of osteoblast precursors is instead suggested to be associated with the anti-catabolic effects. Compared with the individual anabolic therapies, the anabolic therapies that promote the differentiation of BMSC in combination with the anti-MM/anti-catabolic therapies are found to induce a greater increase in the bone volume, while the anabolic therapies that inhibit the apoptosis of active osteoblasts in combination with the anti-MM/anti-catabolic therapies induce a lower increase in the bone volume. The simulations also suggest that the direct inhibition of bortezomib on the osteoclast activity is probably a redundant mechanism.

  2. Oxidatively Degradable Poly(thioketal urethane)/Ceramic Composite Bone Cements with Bone-Like Strength.

    PubMed

    McEnery, Madison A P; Lu, Sichang; Gupta, Mukesh K; Zienkiewicz, Katarzyna J; Wenke, Joseph C; Kalpakci, Kerem N; Shimko, Daniel; Duvall, Craig L; Guelcher, Scott A

    2016-01-01

    Synthetic bone cements are commonly used in orthopaedic procedures to aid in bone regeneration following trauma or disease. Polymeric cements like PMMA provide the mechanical strength necessary for orthopaedic applications, but they are not resorbable and do not integrate with host bone. Ceramic cements have a chemical composition similar to that of bone, but their brittle mechanical properties limit their use in weight-bearing applications. In this study, we designed oxidatively degradable, polymeric bone cements with mechanical properties suitable for bone tissue engineering applications. We synthesized a novel thioketal (TK) diol, which was crosslinked with a lysine triisocyanate (LTI) prepolymer to create hydrolytically stable poly(thioketal urethane)s (PTKUR) that degrade in the oxidative environment associated with bone defects. PTKUR films were hydrolytically stable for up to 6 months, but degraded rapidly (<1 week) under simulated oxidative conditions in vitro. When combined with ceramic micro- or nanoparticles, PTKUR cements exhibited working times comparable to calcium phosphate cements and strengths exceeding those of trabecular bone. PTKUR/ceramic composite cements supported appositional bone growth and integrated with host bone near the bone-cement interface at 6 and 12 weeks post-implantation in rabbit femoral condyle plug defects. Histological evidence of osteoclast-mediated resorption of the cements was observed at 6 and 12 weeks. These findings demonstrate that a PTKUR bone cement with bone-like strength can be selectively resorbed by cells involved in bone remodeling, and thus represent an important initial step toward the development of resorbable bone cements for weight-bearing applications.

  3. Long-term disease-free survival after surgical resection for multiple bone metastases from rectal cancer.

    PubMed

    Choi, Seok Jin; Kim, Jong Hun; Lee, Min Ro; Lee, Chang Ho; Kuh, Ja Hong; Kim, Jung Ryul

    2011-08-10

    Bone metastasis of primary colorectal cancer is uncommon. When it occurs, it is usually a late manifestation of disease and is indicative of poor prognosis. We describe a patient with multiple metachronous bone metastases from lower rectal cancer who was successfully treated with multimodal treatment including surgical resections and has shown 32 mo disease-free survival. Surgical resection of metastatic bone lesion(s) from colorectal cancer may be a good treatment option in selected patients.

  4. Arthroscopic assisted bone grafting for early stages of Kienböck's disease.

    PubMed

    Pegoli, L; Ghezzi, A; Cavalli, E; Luchetti, R; Pajardi, G

    2011-01-01

    Kienböck's disease is known for its difficulty in being diagnosed and treated at early stages; option treatments are few and most of them quite aggressive. The author describes his experience with arthroscopic assisted lunate bone grafting. Three patients with diagnosis of stage I avascular necrosis of the lunate (average age: 45 years), were treated. Before surgical procedure, the patients underwent to a conservative treatment. After harvesting the bone graft from the volar surface of the radius, arthroscopic bone grafting was performed. At an average follow-up of 13.5 months (9-15), all the patients show a normal density of the lunate and no arthritic changes in radiographs. The MRI confirmed the lunate vascularity. The number of patients is definitely small, due also to the rarity of the disease and the difficulty in diagnosis, but, despite the very high learning curve, could be the proper first choice of treatment.

  5. Known VDR polymorphisms are not associated with bone mineral density measures in pediatric Cushing disease.

    PubMed

    Lodish, Maya B; Mastroyannis, Spyridon A; Sinaii, Ninet; Boikos, Sosipatros A; Stratakis, Constantine A

    2012-01-01

    Decreased bone mineral density (BMD) has been documented in adults with Cushing disease (CD), and allelic variants of the vitamin D receptor (VDR) gene have been associated with osteopenia. Genetic factors play an important role in bone accrual and its response to various diseases; among them, the most studied are the allelic variants of the VDR gene. There is debate as to whether described variants in the VDR gene have an effect on BMD. In the current study, we sought to analyze whether BMD differences in patients with CD were associated with the Taq1 and Apal VDR allelotypes. The data showed lack of association between BMD and these widely studied VDR polymorphisms, suggesting that the effect of endogenous hypercortisolism on bone in the context of CD does not depend on VDR genotypes.

  6. Disease Systems Analysis of Bone Mineral Density and Bone Turnover Markers in Response to Alendronate, Placebo, and Washout in Postmenopausal Women

    PubMed Central

    Stone, JA; Verhamme, KM; Danhof, M; Post, TM

    2016-01-01

    A previously established mechanism‐based disease systems model for osteoporosis that is based on a mathematically reduced version of a model describing the interactions between osteoclast (bone removing) and osteoblast (bone forming) cells in bone remodeling has been applied to clinical data from women (n = 1,379) receiving different doses and treatment regimens of alendronate, placebo, and washout. The changes in the biomarkers, plasma bone‐specific alkaline phosphatase activity (BSAP), urinary N‐telopeptide (NTX), lumbar spine bone mineral density (BMD), and total hip BMD, were linked to the underlying mechanistic core of the model. The final model gave an accurate description of all four biomarkers for the different treatments. Simulations were used to visualize the dynamics of the underlying network and the natural disease progression upon alendronate treatment and discontinuation. These results complement the previous applications of this mechanism‐based disease systems model to data from various treatments for osteoporosis. PMID:27869358

  7. Bone marrow fat is increased in chronic kidney disease by magnetic resonance spectroscopy

    PubMed Central

    Fadel, W.; Eckert, G. J.; Ponsler-Sipes, K.; Moe, S. M.; Lin, C.

    2015-01-01

    Summary In aging, the bone marrow fills with fat and this may lead to higher fracture risk. We show that a bone marrow fat measurement by magnetic resonance spectroscopy (MRS), a newer technique not previously studied in chronic kidney disease (CKD), is useful and reproducible. CKD patients have significantly higher bone marrow fat than healthy adults. Introduction Renal osteodystrophy leads to increased morbidity and mortality in patients with CKD. Traditional bone biopsy histomorphometry is used to study abnormalities in CKD, but the bone marrow, the source of osteoblasts, has not been well characterized in patients with CKD. Methods To determine the repeatability of bone marrow fat fraction assessment by MRS and water-fat imaging (WFI) at four sites in patients with CKD, testing was performed to determine the coefficients of reproducibility and intraclass coefficients (ICCs). We further determined if this noninvasive technique could be used to determine if there are differences in the percent bone marrow fat in patients with CKD compared to matched controls using paired t tests. Results The mean age of subjects with CKD was 59.8±7.2 years, and the mean eGFR was 24±8 ml/min. MRS showed good reproducibility at all sites in subjects with CKD and controls, with a coefficient of reproducibilities ranging from 2.4 to 13 %. MRS and WFI assessment of bone marrow fat showed moderate to strong agreement (ICC 0.6–0.7) at the lumbar spine, with poorer agreement at the iliac crest and no agreement at the tibia. The mean percent bone marrow fat at L2–L4 was 13.8 % (95 % CI 8.3–19.7) higher in CKD versus controls (p<0.05). Conclusions MRS is a useful and reproducible technique to study bone marrow fat in CKD. Patients with CKD have significantly higher bone marrow fat than healthy adults; the relationship with bone changes requires further analyses. PMID:25701052

  8. Apoptosis of ileal crypt epithelia after allogeneic bone marrow transplantation without graft-versus-host disease

    PubMed Central

    Kreft, Andreas; Russo, Alexandra; Lux, Steffi; Waiz, Lioudmila; Seidmann, Larissa; Faber, Jörg; Kirkpatrick, Charles J

    2015-01-01

    Key Clinical Message Intestinal crypt cell apoptosis may occur after allogeneic bone marrow transplantation without clinically overt graft-versus-host disease. We describe this phenomenon in a case of a 12-year-old girl who had segments of the ileum resected because of a relapse of acute lymphoblastic leukemia. The diagnostic difficulties are discussed. PMID:25984309

  9. Ollier's Disease of the Iliac Bone with Sacroiliac Joint Involvement in an Adolescent Patient

    PubMed Central

    Koutsouradis, Panagiotis; Skarpidi, Evangelia; Papagelopoulos, Panayiotis J.

    2016-01-01

    Ollier's disease of the hip bone involving the sacroiliac joint has not yet been reported in the English-language literature in both the mature and immature skeletons. The authors present such a unique case in an adolescent girl that posed a significant diagnostic challenge secondary to the rarity of the lesion and atypical clinical picture. PMID:27957379

  10. B-vitamins and bone in health and disease: the current evidence.

    PubMed

    Clarke, M; Ward, M; Strain, J J; Hoey, L; Dickey, W; McNulty, H

    2014-05-01

    Osteoporosis, a metabolic skeletal disease characterised by decreased bone mass and increased fracture risk, is a growing public health problem. Among the various risk factors for osteoporosis, calcium and vitamin D have well-established protective roles, but it is likely that other nutritional factors are also implicated. This review will explore the emerging evidence supporting a role for certain B-vitamins, homocysteine and the 677 C → T polymorphism in the gene encoding the folate-metabolising enzyme methylenetetrahydrofolate reductase, in bone health and disease. The evidence, however, is not entirely consistent and as yet no clear mechanism has been defined to explain the potential link between B-vitamins and bone health. Coeliac disease, a common condition of malabsorption, induced by gluten ingestion in genetically susceptible individuals, is associated with an increased risk both of osteoporosis and inadequate B-vitamin status. Given the growing body of evidence linking low bone mineral density and/or increased fracture risk with low B-vitamin status and elevated homocysteine, optimal B-vitamin status may play an important protective role against osteoporosis in coeliac disease; to date, no trial has addressed this possible link.

  11. Bone Disorders in Chronic Kidney Disease: An Update in Diagnosis and Management.

    PubMed

    Babayev, Revekka; Nickolas, Thomas L

    2015-01-01

    Renal osteodystrophy (ROD) is a bone disorder that occurs in chronic kidney disease (CKD) patients and is associated with 2- to 14-fold increased fracture risk compared to the general population. Risk of fractures is also increased in kidney transplant recipients especially within the first 5 years after transplantation. Fractures in CKD patients are associated with increased morbidity and mortality; thus, proper screening and management of CKD bone complications is critical to improving clinical outcomes. Tetracycline double-labeled transiliac crest bone biopsy with histomorphometry is the gold standard for the diagnosis and classification of ROD. However, bone biopsy is not practical to obtain in all patients. Thus, there is great interest in noninvasive approaches that can be used in the clinic to assess ROD. Here, we discuss the role of surrogate measures of bone health in CKD patients, such as dual energy X-ray absorptiometry (DXA) and novel high-resolution imaging, in conjunction with biochemical biomarkers of bone turnover. Recommended guidelines for diagnosis and management of CKD-MBD are discussed.

  12. Camurati-Engelmann disease in a family from Croatian Island: an old bone scan confirmed pattern of inheritance.

    PubMed

    Baretić, Maja; Korsić, Mirko; Potocki, Kristina; Horvatić, Gordana Herceg; Orlić, Zeljka Crncević

    2014-06-01

    34-year old patient had history of muscular wasting, easy fatigability, pain in extremities and waddling gait since age of four. During the time, neuromuscular disease was suspected, but not confirmed. Elevated bone alkaline phosphatase as well as other bone turnover markers (osteocalcin, procollagen, telopeptide) indicated further skeletal evaluation. Symmetrical enhanced uptake on technetium methylene diphosphonate [99mTc]MPD bone scintigraphy at diaphyses of longitudinal bones and scull matched cortical thickening of long bones and sclerosis of the scull seen at radiograms. Those findings pointed to Camurati-Engelmann disease misdiagnosed for the long time. This rare genetic autosomal dominant disorder was retrospectively diagnosed in asymptomatic father too on the basis of bone scans done long time ago. Old family member scans confirmed heredity pattern of the disease.

  13. Lessons from Microglia Aging for the Link between Inflammatory Bone Disorders and Alzheimer's Disease.

    PubMed

    Wu, Zhou; Nakanishi, Hiroshi

    2015-01-01

    Bone is sensitive to overactive immune responses, which initiate the onset of inflammatory bone disorders, such as rheumatoid arthritis and periodontitis, resulting in a significant systemic inflammatory response. On the other hand, neuroinflammation is strongly implicated in Alzheimer's disease (AD), which can be enhanced by systemic inflammation, such as that due to cardiovascular disease and diabetes. There is growing clinical evidence supporting the concept that rheumatoid arthritis and periodontitis are positively linked to AD, suggesting that inflammatory bone disorders are risk factors for this condition. Recent studies have suggested that leptomeningeal cells play an important role in transducing systemic inflammatory signals to brain-resident microglia. More importantly, senescent-type, but not juvenile-type, microglia provoke neuroinflammation in response to systemic inflammation. Because the prevalence of rheumatoid arthritis and periodontitis increases with age, inflammatory bone disorders may be significant sources of covert systemic inflammation among elderly people. The present review article highlights our current understanding of the link between inflammatory bone disorders and AD with a special focus on microglia aging.

  14. Advances in the understanding of mineral and bone metabolism in inflammatory bowel diseases

    PubMed Central

    Ghishan, Fayez K.

    2011-01-01

    Chronic inflammatory disorders such as inflammatory bowel diseases (IBDs) affect bone metabolism and are frequently associated with the presence of osteopenia, osteoporosis, and increased risk of fractures. Although several mechanisms may contribute to skeletal abnormalities in IBD patients, inflammation and inflammatory mediators such as TNF, IL-1β, and IL-6 may be the most critical. It is not clear whether the changes in bone metabolism leading to decreased mineral density are the result of decreased bone formation, increased bone resorption, or both, with varying results reported in experimental models of IBD and in pediatric and adult IBD patients. New data, including our own, challenge the conventional views, and contributes to the unraveling of an increasingly complex network of interactions leading to the inflammation-associated bone loss. Since nutritional interventions (dietary calcium and vitamin D supplementation) are of limited efficacy in IBD patients, understanding the pathophysiology of osteopenia and osteoporosis in Crohn's disease and ulcerative colitis is critical for the correct choice of available treatments or the development of new targeted therapies. In this review, we discuss current concepts explaining the effects of inflammation, inflammatory mediators and their signaling effectors on calcium and phosphate homeostasis, osteoblast and osteoclast function, and the potential limitations of vitamin D used as an immunomodulator and anabolic hormone in IBD. PMID:21088237

  15. Brittle cornea, blue sclera, and red hair syndrome (the brittle cornea syndrome).

    PubMed Central

    Ticho, U; Ivry, M; Merin, S

    1980-01-01

    A syndrome of red hair, blue sclera, and brittle cornea with recurrent spontaneous perforations is presented in 2 siblings of a Tunisian Jewish family. The genetic transmission of this disorder is autosomal recessive. This is the second description of this syndrome, which should be called the 'brittle cornea syndrome'. This syndrome has so far been reported only in Tunisian Jewish families. Images PMID:7387950

  16. Improvements in Bone Density and Structure during Anti-TNF-α Therapy in Pediatric Crohn's Disease

    PubMed Central

    Thayu, Meena; Baldassano, Robert N.; DeBoer, Mark D.; Zemel, Babette S.; Denburg, Michelle R.; Denson, Lee A.; Shults, Justine; Herskovitz, Rita; Long, Jin; Leonard, Mary B.

    2015-01-01

    Context: Pediatric Crohn's Disease (CD) is associated with deficits in trabecular bone mineral density (BMD) and cortical structure, potentially related to TNF-α effects to decrease bone formation and promote bone resorption. Objective: This study aimed to examine changes in bone density and structure in children and adolescents with CD following initiation of anti-TNF-α therapy. Design and Participants: Participants (n = 74; age 5–21 years) with CD completed a 12-month prospective cohort study. Main Outcome Measures: Tibia peripheral quantitative computed tomography scans were obtained at initiation of anti-TNF-α therapy and 12 months later. Musculoskeletal outcomes were expressed as sex-and race-specific z scores relative to age, based on >650 reference participants. Results: At baseline, CD participants had lower height, trabecular BMD, cortical area (due to smaller periosteal and larger endocortical circumferences), and muscle area z scores, compared with reference participants (all P < .01). Pediatric CD activity index decreased during the 10-week induction (P < .001), in association with subsequent gains in height, trabecular BMD, cortical area (due to recovery of endocortical bone), and muscle area z scores over 12 months (height P < .05; others P < .001). Bone-specific alkaline phosphatase levels, a biomarker of bone formation, increased a median of 75% (P < .001) during induction with associated 12-month improvements in trabecular BMD and cortical area z scores (both P < .001). Younger age was associated with greater increases in trabecular BMD z scores (P < .001) and greater linear growth with greater recovery of cortical area (P < .001). Conclusions: Anti-TNF-α therapy was associated with improvements in trabecular BMD and cortical structure. Improvements were greater in younger and growing participants, suggesting a window of opportunity for treatment of bone deficits. PMID:25919459

  17. International Myeloma Working Group Recommendations for the Treatment of Multiple Myeloma–Related Bone Disease

    PubMed Central

    Terpos, Evangelos; Morgan, Gareth; Dimopoulos, Meletios A.; Drake, Matthew T.; Lentzsch, Suzanne; Raje, Noopur; Sezer, Orhan; García-Sanz, Ramón; Shimizu, Kazuyuki; Turesson, Ingemar; Reiman, Tony; Jurczyszyn, Artur; Merlini, Giampaolo; Spencer, Andrew; Leleu, Xavier; Cavo, Michele; Munshi, Nikhil; Rajkumar, S. Vincent; Durie, Brian G.M.; Roodman, G. David

    2013-01-01

    Purpose The aim of the International Myeloma Working Group was to develop practice recommendations for the management of multiple myeloma (MM) –related bone disease. Methodology An interdisciplinary panel of clinical experts on MM and myeloma bone disease developed recommendations based on published data through August 2012. Expert consensus was used to propose additional recommendations in situations where there were insufficient published data. Levels of evidence and grades of recommendations were assigned and approved by panel members. Recommendations Bisphosphonates (BPs) should be considered in all patients with MM receiving first-line antimyeloma therapy, regardless of presence of osteolytic bone lesions on conventional radiography. However, it is unknown if BPs offer any advantage in patients with no bone disease assessed by magnetic resonance imaging or positron emission tomography/computed tomography. Intravenous (IV) zoledronic acid (ZOL) or pamidronate (PAM) is recommended for preventing skeletal-related events in patients with MM. ZOL is preferred over oral clodronate in newly diagnosed patients with MM because of its potential antimyeloma effects and survival benefits. BPs should be administered every 3 to 4 weeks IV during initial therapy. ZOL or PAM should be continued in patients with active disease and should be resumed after disease relapse, if discontinued in patients achieving complete or very good partial response. BPs are well tolerated, but preventive strategies must be instituted to avoid renal toxicity or osteonecrosis of the jaw. Kyphoplasty should be considered for symptomatic vertebral compression fractures. Low-dose radiation therapy can be used for palliation of uncontrolled pain, impending pathologic fracture, or spinal cord compression. Orthopedic consultation should be sought for long-bone fractures, spinal cord compression, and vertebral column instability. PMID:23690408

  18. Added Value of SPECT/CT in the Evaluation of Benign Bone Diseases of the Appendicular Skeleton.

    PubMed

    Abikhzer, Gad; Srour, Saher; Keidar, Zohar; Bar-Shalom, Rachel; Kagna, Olga; Israel, Ora; Militianu, Daniela

    2016-04-01

    Bone scintigraphy is a sensitive technique to detect altered bone mineralization but has limited specificity. The use of SPECT/CT has improved significantly the diagnostic accuracy of bone scintigraphy, in patients with cancer as well as in evaluation of benign bone disease. It provides precise localization and characterization of tracer-avid foci, shortens the diagnostic workup, and decreases patient anxiety. Through both the SPECT and the CT components, SPECT/CT has an incremental value in characterizing benign bone lesions, specifically in the appendicular skeleton, as illustrated by present case series.

  19. Assessment of metabolic bone diseases by quantitative computed tomography

    SciTech Connect

    Richardson, M.L.; Genant, H.K.; Cann, C.E.; Ettinger, B.; Gordan, G.S.; Kolb, F.O.; Reiser, U.J.

    1985-05-01

    Advances in the radiologic sciences have permitted the development of numerous noninvasive techniques for measuring the mineral content of bone, with varying degrees of precision, accuracy, and sensitivity. The techniques of standard radiography, radiogrammetry, photodensitometry, Compton scattering, neutron activation analysis, single and dual photon absorptiometry, and quantitative computed tomography (QCT) are described and reviewed in depth. Results from previous cross-sectional and longitudinal QCT investigations are given. They then describe a current investigation in which they studied 269 subjects, including 173 normal women, 34 patients with hyperparathyroidism, 24 patients with steroid- induced osteoporosis, and 38 men with idiopathic osteoporosis. Spinal quantitative computed tomography, radiogrammetry, and single photon absorptiometry were performed, and a spinal fracture index was calculated on all patients. The authors found a disproportionate loss of spinal trabecular mineral compared to appendicular mineral in the men with idiopathic osteoporosis and the patients with steroid-induced osteoporosis. They observed roughly equivalent mineral loss in both the appendicular and axial regions in the hyperparathyroid patients. The appendicular cortical measurements correlated moderately well with each other but less well with spinal trabecular QCT. The spinal fracture index correlated well with QCT and less well with the appendicular measurements.

  20. Bone diseases associated with human immunodeficiency virus infection: pathogenesis, risk factors and clinical management.

    PubMed

    Bongiovanni, Marco; Tincati, Camilla

    2006-06-01

    Bone disorders such as osteopenia and osteoporosis have been recently reported in patients infected with the human immunodeficiency virus (HIV), but their etiology remains still unknown. The prevalence estimates vary widely among the different studies and can be affected by concomitant factors such as the overlapping of other possible conditions inducing bone loss as lypodystrophy, advanced HIV-disease, advanced age, low body weight or concomitant use of other drugs. All the reports at the moment available in the literature showed a higher than expected prevalence of reduced bone mineral density (BMD) in HIV-infected subjects both naïve and receiving potent antiretroviral therapy compared to healthy controls. This controversial can suggest a double role played by both antiretroviral drugs and HIV itself due to immune activation and/or cytokines disregulation. An improved understanding of the pathogenesis of bone disorders can result in better preventative and therapeutic measures. However, the clinical relevance and the risk of fractures remains undefined in HIV-population. The clinical management of osteopenia and osteoporosis in HIV-infected subjects is still being evaluated. Addressing potential underlying bone disease risk factors (e.g., smoking and alcohol intake, use of corticosteroids, advanced age, low body weight), evaluating calcium and vitamin D intake, and performing dual x-ray absorptiometry in HIV-infected individuals who have risk factors for bone disease can be important strategies to prevent osteopenia and osteoporosis in this population. The administration of bisphosphonates (e.g., alendronate), with calcium and vitamin D supplementation, may be a reasonable and effective option to treat osteoporosis in these subjects.

  1. Contemporary management of metastatic bone disease: tips and tools of the trade for general practitioners.

    PubMed

    Quinn, Robert H; Randall, R Lor; Benevenia, Joseph; Berven, Sigurd H; Raskin, Kevin A

    2014-01-01

    Metastatic bone disease has a significant effect on a patient's mortality and health-related quality of life. An aging US population and improved survival rates of patients with cancer have led to an increase in the incidence of symptomatic bony metastatic lesions that may require orthopaedic care. Skeletal-related events in neoplastic disease include pain, pathologic fracture, hypercalcemia, and neural compression, including spinal cord compression. The clinical evaluation and diagnostic study of a patient with a skeletal lesion of unknown etiology should be approached carefully. In patients with widespread metastatic disease, the treatment of a skeletal-related event may be limited to stabilization of the pathologic fracture or local disease control. The treatment of metastatic bone disease is guided by the nature of the skeletal-related event, the responsiveness of the lesion to adjuvant care, and the overall condition and survival expectations of the patient. Impending pathologic fractures are often more easily treated, with less morbidity and easier recovery for patients, than completed fractures. Quality of life is the most important outcome measure in these patients. When surgery is indicated, the approach, choice of fixation, and use of adjuvant should allow for immediate and unrestricted weight bearing. Because metastatic lesions to the skeleton have a limited capacity for spontaneous healing, surgical fixation should be durable for the life expectancy of the patient. In the epiphyseal region of long bones, replacement arthroplasty is generally preferred over internal fixation. Metaphyseal and diaphyseal regions can generally be addressed with intramedullary nailing or plate fixation with adjuvant. The specific treatment of acetabular lesions is dictated by the anatomy and the degree of bone loss. Spinal stability and neural compromise are important considerations in choosing a strategy for managing spine tumors. Effective surgical approaches to metastatic

  2. Chemical and biomechanical characterization of hyperhomocysteinemic bone disease in an animal model

    PubMed Central

    Massé, Priscilla G; Boskey, Adele L; Ziv, Israel; Hauschka, Peter; Donovan, Sharon M; Howell, David S; Cole, David EC

    2003-01-01

    Background Classical homocystinuria is an autosomal recessive disorder caused by cystathionine β-synthase (CBS) deficiency and characterized by distinctive alterations of bone growth and skeletal development. Skeletal changes include a reduction in bone density, making it a potentially attractive model for the study of idiopathic osteoporosis. Methods To investigate this aspect of hyperhomocysteinemia, we supplemented developing chicks (n = 8) with 0.6% dl-homocysteine (hCySH) for the first 8 weeks of life in comparison to controls (n = 10), and studied biochemical, biomechanical and morphologic effects of this nutritional intervention. Results hCySH-fed animals grew faster and had longer tibiae at the end of the study. Plasma levels of hCySH, methionine, cystathionine, and inorganic sulfate were higher, but calcium, phosphate, and other indices of osteoblast metabolism were not different. Radiographs of the lower limbs showed generalized osteopenia and accelerated epiphyseal ossification with distinct metaphyseal and suprametaphyseal lucencies similar to those found in human homocystinurics. Although biomechanical testing of the tibiae, including maximal load to failure and bone stiffness, indicated stronger bone, strength was proportional to the increased length and cortical thickness in the hCySH-supplemented group. Bone ash weights and IR-spectroscopy of cortical bone showed no difference in mineral content, but there were higher Ca2+/PO43- and lower Ca2+/CO32- molar ratios than in controls. Mineral crystallization was unchanged. Conclusion In this chick model, hyperhomocysteinemia causes greater radial and longitudinal bone growth, despite normal indices of bone formation. Although there is also evidence for an abnormal matrix and altered bone composition, our finding of normal biomechanical bone strength, once corrected for altered morphometry, suggests that any increase in the risk of long bone fracture in human hyperhomocysteinemic disease is small. We

  3. At the crossroads: EGFR and PTHrP signaling in cancer-mediated diseases of bone

    PubMed Central

    Nickerson, Nicole; Riese, David J.; Hollenhorst, Peter C.; Lorch, Gwendolen; Foley, Anne M.

    2014-01-01

    The epidermal growth factor receptor is a well-established cancer therapeutic target due to its stimulation of proliferation, motility, and resistance to apoptosis. Recently, additional roles for the receptor have been identified in growth of metastases. Similar to development, metastatic spread requires signaling interactions between epithelial-derived tumor cells and mesenchymal derivatives of the microenvironment. This necessitates reactivation of developmental signaling molecules, including the hypercalcemia factor parathyroid hormone-related protein. This review covers the variations of epidermal growth factor receptor signaling in cancers that produce bone metastases, regulation of parathyroid hormone-related protein, and evidence that the two molecules drive cancer-mediated diseases of bone. PMID:22684584

  4. Bilateral Knee Pain Associated with Bone Infarction in a Patient with Behcet's Disease.

    PubMed

    Oktayoglu, Pelin; Cevik, Figen; Tahtasiz, Mehmet; Em, Serda; Bozkurt, Mehtap; Kapukaya, Ahmet; Nas, Kemal

    2012-01-01

    We describe a 31-years-old female patient with severe pain in both knees who had been diagnosed as Behcet's disease (BD) for 12 years. She had had a history of complications due to BD including superior vena cava thrombosis, pulmonary thromboembolism, uveitis, and erythema nodosum and has reported the administration of corticosteroid therapy irregularly. After radiologic evaluation, she has been diagnosed with bone infarction of both left and right knee with the existance of lupus anticoagulants (LA) positivity. Severe joint pain without the evidence of arthritis must alert the clinician to the possibility of bone necrosis of the extremity, although those may rarely occur bilateral in BD.

  5. The consequences of chronic kidney disease on bone metabolism and growth in children

    PubMed Central

    Bacchetta, Justine; Harambat, Jérôme; Cochat, Pierre; Salusky, Isidro B.; Wesseling-Perry, Katherine

    2012-01-01

    Growth retardation, decreased final height and renal osteodystrophy (ROD) are common complications of childhood chronic kidney disease (CKD), resulting from a combination of abnormalities in the growth hormone (GH) axis, vitamin D deficiency, hyperparathyroidism, hypogonadism, inadequate nutrition, cachexia and drug toxicity. The impact of CKD-associated bone and mineral disorders (CKD–MBD) may be immediate (serum phosphate/calcium disequilibrium) or delayed (poor growth, ROD, fractures, vascular calcifications, increased morbidity and mortality). In 2012, the clinical management of CKD–MBD in children needs to focus on three main objectives: (i) to provide an optimal growth in order to maximize the final height with an early management with recombinant GH therapy when required, (ii) to equilibrate calcium/phosphate metabolism so as to obtain acceptable bone quality and cardiovascular status and (iii) to correct all metabolic and clinical abnormalities that can worsen bone disease, growth and cardiovascular disease, i.e. metabolic acidosis, anaemia, malnutrition and 25(OH)vitamin D deficiency. The aim of this review is to provide an overview of the mineral, bone and vascular abnormalities associated with CKD in children in terms of pathophysiology, diagnosis and clinical management. PMID:22851629

  6. [Effect of a single dose of zoledronic acid in a case of Paget bone disease].

    PubMed

    Saban, Melina; Fidalgo, Silvina; Díaz, Carlos A; Lutfi, Ruben J

    2010-01-01

    Paget's disease is a chronic disorder of bone remodeling characterized by increase of bone resorption by atypical osteoclasts, followed by rapid increase in bone formation resulting in a disorganized mosaic bone. The biochemical marker for early diagnosis and monitoring is serum alkaline phosphatase (ALP). We report the case of a 90 year old male, with diagnose of Paget's disease. Pamidronate treatment was started orally with partial response, so it was switched to intravenous pamidronate. Pain intensity and FAL levels diminished. The scyntigraphic scan, however, though improved, persisted abnormal. After several years of treatment, with adequate calcium and vitamin D support, the patient presents pain and increase of FAL. We administered intravenous zoledronic acid (4 mg) in a single dose. After this treatment we observed clinical and biochemical remission during four years and a significantly improvement in the scintigraphy. We report a case of Paget's disease, resistant to pamidronate treatment in whom a single dose of zoledronic acid produced clinical and biochemical remission during 4 years and a significant improvement in the scintigraphic scan.

  7. Aplastic Anemia & MDS International Foundation (AA&MDSIF): Bone Marrow Failure Disease Scientific Symposium 2014.

    PubMed

    Visconte, Valeria; Lindsley, R Coleman; Berlyne, Deborah

    2015-01-01

    Bone marrow failure syndromes (BMFS) are characterized by a failure of the hematopoietic stem cells to produce adequate blood cells, resulting in either cytopenia (defect in one or more blood cell lineages) or pancytopenia (defect in all blood cell lineages). BMFS can be inherited or acquired. The pathogenesis of these diseases is very heterogeneous. Research efforts have been made all over the world to improve the basic knowledge of these diseases. The Aplastic Anemia and MDS International Foundation (AA&MDSIF) is an independent nonprofit organization whose mission is to help patients and family members cope with BMFS. Here, we summarize novel scientific discoveries in several BMFS that were presented at the 4th International Bone Marrow Failure Disease Scientific Symposium 2014 that AA&MDSIF sponsored on March 27-28, 2014, in Rockville, MD.

  8. Laser technologies in treatment of degenerative-dystrophic bone diseases in children

    NASA Astrophysics Data System (ADS)

    Abushkin, Ivan A.; Privalov, Valery A.; Lappa, Alexander V.; Noskov, Nikolay V.; Neizvestnykh, Elena A.; Kotlyarov, Alexander N.; Shekunova, Yulia G.

    2014-03-01

    Two low invasive laser technologies for treatment of degenerative-dystrophic bone diseases in children are presented. The first is the transcutaneous laser osteoperforation developed by us and initially applied for treatment of different inflammatory and traumatic diseases (osteomyelitides, osteal and osteoarticular panaritiums, delayed unions, false joints, and others). Now the technology was applied to treatment of aseptic osteonecrosis of different localizations in 134 children aged from 1 to 16 years, including 56 cases with necrosis of femoral head (Legg-Calve-Perthes disease), 42 with necrosis of 2nd metatarsal bone head (Kohler II disease), and 36 with necrosis of tibial tuberosity (Osgood-Schlatter disease). The second technology is the laser intracystic thermotherapy for treatment of bone cysts. The method was applied to 108 children aged from 3 to 16 years with aneurismal and solitary cysts of different localizations. In both technologies a 970 nm diode laser was used. The suggested technologies increase the efficiency of treatment, reduce its duration, can be performed on outpatient basis, which resulted in great economical effect.

  9. Absence of measles virus and canine distemper virus transcripts in long-term bone marrow cultures from patients with Paget's disease of bone.

    PubMed

    Ooi, C G; Walsh, C A; Gallagher, J A; Fraser, W D

    2000-09-01

    The presence of intranuclear inclusions in pagetic osteoclasts with similar characteristics to those seen in some slow viral diseases has lead to the hypothesis that Paget's disease is caused by a similar infection. Bone marrow aspirates from seven patients with hemipelvic Paget's disease were taken from both sides of the pelvis and cultured under identical conditions. RNA was extracted after approximately 2 weeks of culture and reverse transcriptase-linked polymerase chain reaction used to investigate the expression of measles and canine distemper virus RNA. We were unable to detect the presence of measles virus (MV) or canine distemper virus (CDV) transcripts in bone marrow cultures from either affected or unaffected sites in any of our patients. The results of this study do not support a role for MV or CDV in the pathogenesis of Paget's disease of bone.

  10. Brittle damage models in DYNA2D

    SciTech Connect

    Faux, D.R.

    1997-09-01

    DYNA2D is an explicit Lagrangian finite element code used to model dynamic events where stress wave interactions influence the overall response of the system. DYNA2D is often used to model penetration problems involving ductile-to-ductile impacts; however, with the advent of the use of ceramics in the armor-anti-armor community and the need to model damage to laser optics components, good brittle damage models are now needed in DYNA2D. This report will detail the implementation of four brittle damage models in DYNA2D, three scalar damage models and one tensor damage model. These new brittle damage models are then used to predict experimental results from three distinctly different glass damage problems.

  11. [Pain control of bone and joint diseases in the elderly].

    PubMed

    Soen, Satoshi

    2014-10-01

    The decline of multiple physiological processes, even in the absence of disease, combined should logically influence treatment options. Decreased gastric secretions, intestinal motility, and vitamin D receptors lead to loss of appetite, malnutrition. Increased arterial thickening and rigidity elevate cardiac risk, while decreased elasticity in the lungs potentially exacerbates breathing disorders. Memory impairment and cognitive decline progress as neurons become less resilient to stress over time. Reduced hepatic and renal blood flow limit metabolism and filtration, increasing the risk for accumulation of toxic substances. Physiologic changes, drug-drug interactions resulting from polypharmacy, and drug-disease interactions combine to make elderly patients more sensitive to the AEs of medications. Effective pain management in the elderly is challenging. The purpose of this review is to highlight the use of several treatment options for elderly patients.

  12. Untreated Paget disease of bone studied by scintigraphy

    SciTech Connect

    Vellenga, C.J.L.R.; Pauwels, E.K.J.; Bijvoet, O.L.M.; Frijlink, W.B.; Mulder, J.D.; Hermans, J.

    1984-12-01

    The authors determined that the concentration of radioactivity in a lesion of Paget disease correlates with the grade of radiological deformation and the frequency of pain; the total skeletal uptake correlates with the severity of the biochemical abnormalities. They suggest that the major determinant of uptake in untreated lesions is abnormal metabolic activity, and in lesions in remission it is structural deformation of mineralized tissue. It is likely that the metabolic activity, and possibly also the rate of progression of the individual lesions, will differ in the individual patient, and that metabolic activity determines the amount of deformation and the chance of pain. Lesions not visible on the radiograph usually show only low uptake of Tc-99m-Sn-EHDP; the majority of these lesions are asymptomatic and reflect low activity of the disease. Radiological differentiation between sclerotic and osteolytic lesions does not reflect differences in either scintigraphic uptake, metabolic acitivity, or pain.

  13. Calcium and vitamin D nutrition and bone disease of the elderly.

    PubMed

    Gennari, C

    2001-04-01

    Osteoporosis, a systemic skeletal disease characterized by a low bone mass, is a major public health problem in EC member states because of the high incidence of fragility fractures, especially hip and vertebral fracture. In EC member states the high incidence of osteoporotic fractures leads to considerable mortality, morbidity, reduced mobility and decreased quality of life. In 1995 the number of hip fractures in 15 countries of EC has been 382,000 and the estimated total care cost of about 9 billion of ECUs. Given the magnitude of the problem public health measures are important for preventive intervention. Skeletal bone mass is determined by a combination of endogenous (genetic, hormonal) and exogenous (nutritional, physical activity) factors. Nutrition plays an important role in bone health. The two nutrients essential for bone health are calcium and vitamin D. Reduced supplies of calcium are associated with a reduced bone mass and osteoporosis, whereas a chronic and severe vitamin D deficiency leads to osteomalacia, a metabolic bone disease characterized by a decreased mineralization of bone. Vitamin D insufficiency, the preclinical phase of vitamin D deficiency, is most commonly found in the elderly. The major causes of vitamin D deficiency and insufficiency are decreased renal hydroxylation of vitamin D, poor nutrition, scarce exposition to sunlight and a decline in the synthesis of vitamin D in the skin. The daily average calcium intake in Europe has been evaluated in the SENECA study concerning the diet of elderly people from 19 towns of 10 European countries. In about one third of subjects the dietary calcium intake results were very low, between 300 and 600 mg/day in women, and 350 and 700 mg/day in men. Calcium supplements reduce the rate of bone loss in osteoporotic patients. Some recent studies have reported a significant positive effect of calcium treatment not only on bone mass but also on fracture incidence. The SENECA study, has also shown that

  14. High Speed Dynamics in Brittle Materials

    NASA Astrophysics Data System (ADS)

    Hiermaier, Stefan

    2015-06-01

    Brittle Materials under High Speed and Shock loading provide a continuous challenge in experimental physics, analysis and numerical modelling, and consequently for engineering design. The dependence of damage and fracture processes on material-inherent length and time scales, the influence of defects, rate-dependent material properties and inertia effects on different scales make their understanding a true multi-scale problem. In addition, it is not uncommon that materials show a transition from ductile to brittle behavior when the loading rate is increased. A particular case is spallation, a brittle tensile failure induced by the interaction of stress waves leading to a sudden change from compressive to tensile loading states that can be invoked in various materials. This contribution highlights typical phenomena occurring when brittle materials are exposed to high loading rates in applications such as blast and impact on protective structures, or meteorite impact on geological materials. A short review on experimental methods that are used for dynamic characterization of brittle materials will be given. A close interaction of experimental analysis and numerical simulation has turned out to be very helpful in analyzing experimental results. For this purpose, adequate numerical methods are required. Cohesive zone models are one possible method for the analysis of brittle failure as long as some degree of tension is present. Their recent successful application for meso-mechanical simulations of concrete in Hopkinson-type spallation tests provides new insight into the dynamic failure process. Failure under compressive loading is a particular challenge for numerical simulations as it involves crushing of material which in turn influences stress states in other parts of a structure. On a continuum scale, it can be modeled using more or less complex plasticity models combined with failure surfaces, as will be demonstrated for ceramics. Models which take microstructural

  15. Efficacy and safety of bisphosphonates in management of low bone density in inflammatory bowel disease

    PubMed Central

    Yao, Liwei; Wang, Haiqing; Dong, Wenwei; Liu, Zhenxin; Mao, Haijiao

    2017-01-01

    Abstract This study aims to determine whether bisphosphonates are safe, as well as effective against bone mineral loss in inflammatory bowel disease (IBD). A computerized search of electronic databases from 1966 to 2016 was performed. Randomized controlled trials (RCTs) were included in this review to evaluate the role of bisphosphonates in the management of osteoporosis in IBD patients. A revised 7-point Jadad scale was used to evaluate the quality of each study. Overall, 13 RCTs and 923 patients met the inclusion criteria of this meta-analysis. The result showed that bisphosphonates decreased bone mass density (BMD) loss at the lumbar spine (P = 0.0002), reduced the risk of new fractures (P = 0.01), and retained the similar adverse events (P = 0.86). Bisphosphonates may provide protection and safety against bone mineral loss in IBD patients. PMID:28099343

  16. Granulomatous bone marrow disease. A review of the literature and clinicopathologic analysis of 58 cases.

    PubMed

    Bodem, C R; Hamory, B H; Taylor, H M; Kleopfer, L

    1983-11-01

    We have reviewed 58 cases of bone marrow granuloma at a single institution over a 20-year time span, and have summarized the available English literature. We conclude that bone marrow granulomas are an infrequent pathologic finding which, when found, require definition as to an underlying etiology. Undoubtedly, the illnesses associated with marrow granuloma are similar to those causing granulomatous hepatitis. The following additional statements may justifiably be made based on this review. There are no morphologic features which allow reliable differentiation between the causes of bone marrow granuloma. By combining careful histologic, microbiologic, and serologic techniques, an etiology can be documented in most (87%) patients with marrow granulomas. A medication history is an important element of this evaluation. Rocky Mountain spotted fever, cytomegalovirus infection, ibuprofen, acute lymphocytic leukemia, and various collagen vascular diseases should be added to the list of causes of marrow granuloma. The prognostic significance of marrow granuloma in patients without an ascertainable underlying illness remains unclear.

  17. Clinical utility of a wheat-germ precipitation assay for determination of bone alkaline phosphatase concentrations in patients with different metabolic bone diseases.

    PubMed

    Braga, V; Dorizzi, R; Brocco, G; Rossini, M; Zamberlan, N; Gatti, D; Adami, S

    1995-07-01

    Bone alkaline phosphatase was evaluated by wheat-germ lectin precipitation in several clinical conditions. The study included 33 premenopausal healthy women, 46 postmenopausal apparently healthy women, 19 growing children, 24 patients with Paget's disease, 31 patients with primary hyperparathyroidism and 66 patients with hepatobiliary diseases. In postmenopausal women the mean T score (i.e.: the number of SD below or above the mean for premenopausal women) was 2.6 +/- 1.3 (SD) for bone alkaline phosphatase and 1.61 +/- 1.21 for total alkaline phosphatase (p < 0.001). The T score for bone alkaline phosphatase provided a better discrimination from normals for both Paget's disease (22.1 +/- 27.8 versus 12.8 +/- 16 p < 0.001) and primary hyperparathyroidism (8.2 +/- 4.3 versus 4.6 +/- 3.7 p < 0.005 for bone alkaline phosphatase and total alkaline phosphatase respectively). After treatment with intravenous bisphosphonate the percent decrease of bone alkaline phosphatase was larger than that of total alkaline phosphatase both in patients with Paget's disease (-46% versus -72% p < 0.01) and in patients with primary hyperparathyroidism (-21% versus -47% p < 0.02) and an estimate of the precision (delta mean/SD of the delta mean) for bone alkaline phosphatase was 1.9-3.7 times higher than that of total alkaline phosphatase. In twelve osteoporotic patients treated for six months with oral alendronate the decrease in bone turnover was detected with significantly higher precision with bone alkaline phosphatase than with total alkaline phosphatase (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Serum albumin and body weight as biomarkers for the antemortem identification of bone and gastrointestinal disease in the common marmoset.

    PubMed

    Baxter, Victoria K; Shaw, Gillian C; Sotuyo, Nathaniel P; Carlson, Cathy S; Olson, Erik J; Zink, M Christine; Mankowski, Joseph L; Adams, Robert J; Hutchinson, Eric K; Metcalf Pate, Kelly A

    2013-01-01

    The increasing use of the common marmoset (Callithrix jacchus) in research makes it important to diagnose spontaneous disease that may confound experimental studies. Bone disease and gastrointestinal disease are two major causes of morbidity and mortality in captive marmosets, but currently no effective antemortem tests are available to identify affected animals prior to the terminal stage of disease. In this study we propose that bone disease and gastrointestinal disease are associated disease entities in marmosets and aim to establish the efficacy of several economical antemortem tests in identifying and predicting disease. Tissues from marmosets were examined to define affected animals and unaffected controls. Complete blood count, serum chemistry values, body weight, quantitative radiographs, and tissue-specific biochemical markers were evaluated as candidate biomarkers for disease. Bone and gastrointestinal disease were associated, with marmosets being over seven times more likely to have either concurrent bone and gastrointestinal disease or neither disease as opposed to lesions in only one organ system. When used in tandem, serum albumin <3.5 g/dL and body weight <325 g identified 100% of the marmosets affected with concurrent bone and gastrointestinal disease. Progressive body weight loss of 0.05% of peak body weight per day predicted which marmosets would develop disease prior to the terminal stage. Bone tissue-specific tests, such as quantitative analysis of radiographs and serum parathyroid hormone levels, were effective for distinguishing between marmosets with bone disease and those without. These results provide an avenue for making informed decisions regarding the removal of affected marmosets from studies in a timely manner, preserving the integrity of research results.

  19. [Acute renal failure secondary to hepatic veno-occlusive disease in a bone marrow transplant patient].

    PubMed

    Borrego, F J; Viedma, G; Pérez del Barrio, P; Gil, J M; de Santis-Scoccia, C; Ramírez Huerta, J M; Alcalá, A; Pérez Bañasco, V

    2003-01-01

    Acute renal failure following bone marrow transplantation is a frequent complication with an incidence ranging 15-30% and with high rates of morbidity and mortality. Numerous potential etiologies can be implicated as chemotherapy regimen, use of nephrotoxic antibiotics, sepsis-induced damage, cyclosporine toxicity and other especific pathologies as graft-v-host disease or veno-occlusive disease of the liver. We report the case of a 41-year-old man who underwent autologous peripheral blood stem cell transplantation and developed and acute renal failure secondary to a fatal veno-occlusive disease of the liver. Incidence, potential predisposing factors, outcome and possibilities of treatment are reviewed.

  20. [Animal models for bone and joint disease. CIA, CAIA model].

    PubMed

    Hirose, Jun; Tanaka, Sakae

    2011-02-01

    The collagen-induced arthritis (collagen-induced arthritis, CIA) is an autoimmune arthritis that resembles rheumatoid arthritis (RA) in many ways, therefore it has been used most commonly as a model of RA. CIA is induced by immunization with an emulsion of complete Freund's adjuvant (CFA) and type II collagen (C II ) . Collagen antibody-induced arthritis (CAIA) is induced by the administration of a cocktail of monoclonal antibodies recognizing conserved epitopes located within the CB11 fragment. CAIA offers several advantages over CIA, including rapid disease onset, high uptake rate, and the capacity to use genetically modified mice, such as transgenics and knockouts.

  1. The role of Dickkopf-1 in bone development, homeostasis, and disease.

    PubMed

    Pinzone, Joseph J; Hall, Brett M; Thudi, Nanda K; Vonau, Martin; Qiang, Ya-Wei; Rosol, Thomas J; Shaughnessy, John D

    2009-01-15

    Wnt/beta-catenin signaling is central to bone development and homeostasis in adulthood and its deregulation is associated with bone pathologies. Dickkopf-1 (DKK1), a soluble inhibitor of Wnt/beta-catenin signaling required for embryonic head development, regulates Wnt signaling by binding to the Wnt coreceptor lipoprotein-related protein-5 (LRP5)/Arrow. LRP5 mutations causing high bone mass syndromes disrupt DKK1-mediated regulation of LRP5. Forced overexpression of Dkk1 in osteoblasts causes osteopenia, disruption of the hematopoietic stem cell (HSC) niche, and defects in HSC function. Dkk1 also inhibits fracture repair. Studies suggest that DKK1 activation in osteoblasts is the underlying cause of glucocorticoid- and estrogen deficiency-mediated osteoporosis, and at least partially underlies the teratogenic effects of thalidomide on limb development. DKK1 induces proliferation of mesenchymal stem cells (MSC) in vitro and may play a role in the development of high-grade undifferentiated pleomorphic sarcomas derived from MSC and osteosarcomas. DKK1 has been implicated in causing erosive arthritis, the osteolytic phenotypes of multiple myeloma and metastatic breast cancer, and osteoblastic metastases of prostate cancer. Preclinical studies have shown that neutralizing DKK1/Dkk1 and/or enhancing Wnt/beta-catenin signaling may prove effective in treating bone pathologies. Here, we review the rapidly growing body of literature defining a pivotal role for DKK1 in bone health and disease.

  2. [Bone and joint decade--"mile step" in diagnostics and treatment of movement system diseases?].

    PubMed

    Brongel, Leszek; Lorkowski, Jacek; Hładki, Waldemar; Trybus, Marek

    2006-01-01

    Musculoskeletal disorders affect hundreds of millions of people across the world and are the most common causes of severe long-term pain and physical disability. The impact from such disorders on the individual and on society let to propose by WHO for the Decade of the Bone and Joint from 2000 to 2010. The goal of the Decade is to improve the health-related quality of life for people with musculoskeletal disorders throughout the world and this could be achieved by raising awareness of the growing burden of bone and joint diseases on society, promoting prevention and treatment and advancing understanding of musculoskeletal disorders through research. The main fields of interest during the Decade are joint diseases, spinal disorders and low back pain, osteoporosis and severe trauma of the extremities. In our Department we study problems concerning on traumatology of old patients, multitrauma injury, biomechanics in spinal disorders, in degenerative joint disease and foot diseases. Apart from contemporary imaging methods like US or CT we use pedobarographic diagnostics and fotogrammetric examination. In this study we present strategic goals and the summary of our ongoing projects in our Department related to the goals of the Bone and Joint Decade.

  3. FGF23 neutralization improves bone quality and osseointegration of titanium implants in chronic kidney disease mice.

    PubMed

    Sun, Ningyuan; Guo, Yuchen; Liu, Weiqing; Densmore, Michael; Shalhoub, Victoria; Erben, Reinhold G; Ye, Ling; Lanske, Beate; Yuan, Quan

    2015-02-10

    Chronic kidney disease (CKD) is a worldwide health problem. Serum levels of FGF23, a phosphaturic hormone, increase at the earliest stages of CKD, and have been found to be independently associated with the mortality and morbidity of CKD patients. The purpose of this study was to evaluate whether FGF23 neutralization was able to improve bone quality and osseointegration of titanium implants. Uremia was induced by 5/6 nephrectomy in adult female mice. Postsurgery, the mice were injected with vehicle or FGF23 neutralizing antibody (5 mg/kg body weight) 3 times a week. Experimental titanium implants were inserted in the distal end of the femurs. FGF23 neutralization significantly increased serum phosphate, 1,25(OH)2D and BUN, and decreased serum PTH and FGF23, relative to vehicle-treated CKD mice. Histomorphometric analysis of the tibiae indicated that FGF23 neutralization normalized the osteoidosis observed in vehicle-treated CKD mice. Although bone-implant contact ratio remained unchanged by anti-FGF23 antibody treatment, the strength of osseointegration, as evidenced by a biomechanical push-in test, was significantly improved by FGF23 neutralization. Our findings revealed that FGF23 neutralization effectively improves bone quality and osseointegration of titanium implants in CKD mice, suggesting FGF23 as a key factor of CKD related bone diseases.

  4. [Occult involvement of bone marrow in Hodgkin's disease: detection with magnetic resonance].

    PubMed

    Sanz, L; Cervantes, F; Mercader, J M; Rozman, M; Rozman, C; Montserrat, E

    1996-06-22

    Although bone marrow biopsy is considered the best procedure to detect bone marrow involvement by Hodgkin's disease (HD), in recent years several studies have emphasized the value of magnetic resonance imaging (MRI). We present the case of a patient with HD apparently localized in a laterocervical lymph node, who also referred disestasiae at a region corresponding to D10 metamera. Bone marrow biopsy, vertebral TC and 67-Ga scintigraphy were all normal. However, a node of 1 cm in diameter was detected by MRI in the tenth dorsal vertebra. Because of the topographic coincidence between the patient's symptomatology and the MRI findings, the HD was considered to be in advanced stage and CMOPP/ABV chemotherapy was administered, this resulting in a rapid improvement of symptoms and disappearance of the MRI abnormalities. Since in the present case, the MRI determined a change in disease stage and treatment, the role of MRI as a complementary exploration of bone marrow biopsy to detect marrow involvement by HD is reviewed.

  5. Odanacatib, A Cathepsin K-Specific Inhibitor, Inhibits Inflammation and Bone Loss Caused by Periodontal Diseases

    PubMed Central

    Hao, Liang; Chen, Jianwei; Zhu, Zheng; Reddy, Michael S.; Mountz, John D.; Chen, Wei; Li, Yi-Ping

    2015-01-01

    Background Periodontitis is a bacteria-induced inflammatory disease mainly affecting periodontal tissues, leading to periodontal inflammation, bone breakdown, and loss of the tooth. The main obstacle for treating periodontitis effectively is the difficulty in finding a target that can inhibit bone loss and inflammation simultaneously. Recent studies showed that cathepsin K (CTSK) might have functions in the immune system besides its role in osteoclasts. Thus, targeting CTSK would have a potential therapeutic effect in both the bone system and the immune system during the progression of periodontitis. Methods In the current study, a small molecular inhibitor (odanacatib [ODN]) is explored to inhibit the function of CTSK in a bacteria-induced periodontitis mouse model. Results The application of ODN decreased the number of osteoclasts, macrophages, and T cells, as well as the expression of Toll-like receptors (TLRs) in the periodontitis lesion area. Furthermore, lack of CTSK inhibited the expression of TLR4, TLR5, and TLR9 and their downstream cytokine signaling in the gingival epithelial cells in periodontitis lesions, demonstrating that the innate immune response was inhibited in periodontitis. Conclusion The present results show that inhibition of CTSK can prevent bone loss and the immune response during the progression of periodontitis, indicating that CTSK is a promising target for treating inflammatory diseases such as periodontitis by affecting both osteoclasts and the immune system. PMID:25879791

  6. Ductile to brittle transition in dynamic fracture of brittle bulk metallic glass

    SciTech Connect

    Wang, G.; Han, Y. N.; Han, B. S.; Wang, W. H.; Xu, X. H.; Ke, F. J.

    2008-05-01

    We report an unusual transition from a locally ductile to a pure brittle fracture in the dynamic fracture of brittle Mg{sub 65}Cu{sub 20}Gd{sub 10} bulk metallic glass. The fractographic evolution from a dimple structure to a periodic corrugation pattern and then to the mirror zone along the crack propagation direction during the dynamic fracture process is discussed within the framework of the meniscus instability of the fracture process zone. This work might provide an important clue in understanding of the energy dissipation mechanism for dynamic crack propagation in brittle glassy materials.

  7. Multitracer Molecular Imaging of Paget Disease Targeting Bone Remodeling, Fatty Acid Metabolism, and PSMA Expression on PET/CT.

    PubMed

    Derlin, Thorsten; Weiberg, Desiree; Sohns, Jan M

    2016-12-01

    Paget disease is a chronic disorder resulting in enlarged and misshapen bones, and is caused by disorganized bone remodeling. We present the case of an 85-year-old man with prostatic adenocarcinoma and known Paget disease of the right iliac bone who underwent Ga-prostate-specific membrane antigen ligand, C-acetate, and F-fluoride PET/CT for restaging of cancer. On all PET scans, increased tracer accumulation was observed in Paget disease of bone. Besides that Paget disease may mimic metastases on PET/CT using various radiotracers, including Ga-prostate-specific membrane antigen ligands and C-acetate, this case highlights the potential of multiparametric disease characterization on PET.

  8. Brittle Books Programs. SPEC Kit 152.

    ERIC Educational Resources Information Center

    Merrill-Oldham, Jan; Walker, Gay

    This document focuses on the evaluation, bibliographic searching, replacement, preservation photocopying, and microfilming of library materials that are too brittle to handle without risking damage. To assess these activities, a SPEC (Systems and Procedures Exchange Center) survey was sent to members of the Association of Research Libraries (ARL),…

  9. Precision grinding process development for brittle materials

    SciTech Connect

    Blaedel, K L; Davis, P J; Piscotty, M A

    1999-04-01

    High performance, brittle materials are the materials of choice for many of today's engineering applications. This paper describes three separate precision grinding processes developed at Lawrence Liver-more National Laboratory to machine precision ceramic components. Included in the discussion of the precision processes is a variety of grinding wheel dressing, truing and profiling techniques.

  10. The gradient deformation criterion for brittle fracture

    NASA Astrophysics Data System (ADS)

    Kuliev, V. D.; Morozov, E. M.

    2016-10-01

    A new fracture criterion based on the assumption that brittle fracture occurs when the strain gradient reaches its limiting value is formulated. The presence of a strain gradient at the boundary of a body's temperature drop is shown analytically. The results of an experiment with specimens under an abrupt change in temperature are presented.

  11. External fixation and cancellous bone grafting for Kienböck's disease: a preliminary report.

    PubMed

    Zelouf, D S; Ruby, L K

    1996-09-01

    Between 1985 and 1990, 17 patients with histologically proven Kienböck's disease (Lichtman stages I, II, and III) underwent a combination of cancellous bone grafting to the lunate and external fixation across the wrist. All 17 patients were available for review with a minimum follow-up of 2 years (average, 47 years). Based on pain, functional status, range of motion, and grip strength (Mayo wrist score), there were 6 excellent, 6 good, 2 fair, and 3 poor results (2 of whom required further surgery). An overall success rate of 71% (12 of 17) was achieved. Ten patients underwent postoperative magnetic resonance scanning, and in 5, some improvement in signal intensity was demonstrated. The combination of cancellous bone grafting and external fixation is an alternative treatment for Kienböck's disease.

  12. Bone Marrow-Derived Cells as a Therapeutic Approach to Optic Nerve Diseases

    PubMed Central

    Mesentier-Louro, Louise A.; Zaverucha-do-Valle, Camila; Rosado-de-Castro, Paulo H.; Silva-Junior, Almir J.; Pimentel-Coelho, Pedro M.; Mendez-Otero, Rosalia; Santiago, Marcelo F.

    2016-01-01

    Following optic nerve injury associated with acute or progressive diseases, retinal ganglion cells (RGCs) of adult mammals degenerate and undergo apoptosis. These diseases have limited therapeutic options, due to the low inherent capacity of RGCs to regenerate and due to the inhibitory milieu of the central nervous system. Among the numerous treatment approaches investigated to stimulate neuronal survival and axonal extension, cell transplantation emerges as a promising option. This review focuses on cell therapies with bone marrow mononuclear cells and bone marrow-derived mesenchymal stem cells, which have shown positive therapeutic effects in animal models of optic neuropathies. Different aspects of available preclinical studies are analyzed, including cell distribution, potential doses, routes of administration, and mechanisms of action. Finally, published and ongoing clinical trials are summarized. PMID:26649049

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

    NASA Astrophysics Data System (ADS)

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

    2015-02-01

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

  14. European origin of patients with Paget's disease of bone in the Buenos Aires area.

    PubMed

    Gómez Acotto, C; Mautalen, C A

    2001-01-01

    Paget's bone disease is heterogeneously distributed and several foci of high prevalence have been reported in Europe, United States, Argentina and Australia. The aim of the present work was to determine the ethnic origin of the disease in Buenos Aires using a cross sectional epidemiological study. Sample choice was based on a sampling according to grandparents' nationality. Ninety five percent of Paget patients were of European descent and 5% were non-European, while in the control group the proportion of European descendants is lower: 83% (OR: 3.7; p < 0.007; IC 95%: 1.4-9.7). Within the group of patients with Paget's disease the proportion of Italian and Russian descendants was higher than expected according to the 1914 Argentinean census. The prevalence of Paget's disease among European migrants was higher than in the control group of citizens. Regardless of environmental factors, it is likely that the migrants carried a higher risk of developing the disease.

  15. Cortical-Bone Fragility — Insights from sFRP4 Deficiency in Pyle’s Disease

    PubMed Central

    Unger, Sheila; Hesse, Eric; Yamana, Kei; Kiviranta, Riku; Solban, Nicolas; Liu, Jeff; Brommage, Robert; Boduroglu, Koray; Bonafé, Luisa; Campos-Xavier, Belinda; Dikoglu, Esra; Eastell, Richard; Gossiel, Fatma; Harshman, Keith; Nishimura, Gen; Girisha, Katta M.; Stevenson, Brian J.; Takita, Hiroyuki; Rivolta, Carlo

    2016-01-01

    BACKGROUND Cortical-bone fragility is a common feature in osteoporosis that is linked to nonvertebral fractures. Regulation of cortical-bone homeostasis has proved elusive. The study of genetic disorders of the skeleton can yield insights that fuel experimental therapeutic approaches to the treatment of rare disorders and common skeletal ailments. METHODS We evaluated four patients with Pyle’s disease, a genetic disorder that is characterized by cortical-bone thinning, limb deformity, and fractures; two patients were examined by means of exome sequencing, and two were examined by means of Sanger sequencing. After a candidate gene was identified, we generated a knockout mouse model that manifested the phenotype and studied the mechanisms responsible for altered bone architecture. RESULTS In all affected patients, we found biallelic truncating mutations in SFRP4, the gene encoding secreted frizzled-related protein 4, a soluble Wnt inhibitor. Mice deficient in Sfrp4, like persons with Pyle’s disease, have increased amounts of trabecular bone and unusually thin cortical bone, as a result of differential regulation of Wnt and bone morphogenetic protein (BMP) signaling in these two bone compartments. Treatment of Sfrp4-deficient mice with a soluble Bmp2 receptor (RAP-661) or with antibodies to sclerostin corrected the cortical-bone defect. CONCLUSIONS Our study showed that Pyle’s disease was caused by a deficiency of sFRP4, that cortical-bone and trabecular-bone homeostasis were governed by different mechanisms, and that sFRP4-mediated cross-regulation between Wnt and BMP signaling was critical for achieving proper cortical-bone thickness and stability. (Funded by the Swiss National Foundation and the National Institutes of Health.) PMID:27355534

  16. Role of Bruton’s tyrosine kinase in myeloma cell migration and induction of bone disease

    PubMed Central

    Bam, Rakesh; Ling, Wen; Khan, Sharmin; Pennisi, Angela; Venkateshaiah, Sathisha Upparahalli; Li, Xin; van Rhee, Frits; Usmani, Saad; Barlogie, Bart; Shaughnessy, John; Epstein, Joshua; Yaccoby, Shmuel

    2014-01-01

    Myeloma cells typically grow in bone, recruit osteoclast precursors and induce their differentiation and activity in areas adjacent to tumor foci. Bruton’s tyrosine kinase (BTK), of the TEC family, is expressed in hematopoietic cells and is particularly involved in B-lymphocyte function and osteoclastogenesis. We demonstrated BTK expression in clinical myeloma plasma cells, interleukin (IL) –6– or stroma–dependent cell lines and osteoclasts. SDF-1 induced BTK activation in myeloma cells and BTK inhibition by small hairpin RNA or the small molecule inhibitor, LFM-A13, reduced their migration toward stromal cell-derived factor-1 (SDF-1). Pretreatment with LFM-A13 also reduced in vivo homing of myeloma cells to bone using bioluminescence imaging in the SCID-rab model. Enforced expression of BTK in myeloma cell line enhanced cell migration toward SDF-1 but had no effect on short-term growth. BTK expression was correlated with cell-surface CXCR4 expression in myeloma cells (n = 33, r = 0.81, P < 0.0001), and BTK gene and protein expression was more profound in cell-surface CXCR4-expressing myeloma cells. BTK was not upregulated by IL-6 while its inhibition had no effect on IL-6 signaling in myeloma cells. Human osteoclast precursors also expressed BTK and cell-surface CXCR4 and migrated toward SDF-1. LFM-A13 suppressed migration and differentiation of osteoclast precursors as well as bone-resorbing activity of mature osteoclasts. In primary myeloma-bearing SCID-rab mice, LFM-A13 inhibited osteoclast activity, prevented myeloma-induced bone resorption and moderately suppressed myeloma growth. These data demonstrate BTK and cell-surface CXCR4 association in myeloma cells and that BTK plays a role in myeloma cell homing to bone and myeloma-induced bone disease. PMID:23456977

  17. Bone mineral density and vitamin D status in Parkinson's disease patients.

    PubMed

    van den Bos, F; Speelman, A D; van Nimwegen, M; van der Schouw, Y T; Backx, F J G; Bloem, B R; Munneke, M; Verhaar, H J J

    2013-03-01

    Bone loss is more common in Parkinson's disease (PD) than in the general population. Several factors may be involved in the development of bone loss, including malnutrition, immobilization, low body mass index, decreased muscle strength, vitamin D deficiency and medication use. This study investigates the prevalence of osteoporosis and possible risk factors associated with bone loss in early stage PD. In 186 PD patients (Hoehn and Yahr stage 1-2.5, mean age 64.1 years, 71 % men) bone mineral density (BMD) measurements were performed with DEXA. T- and Z-scores were calculated. Univariate linear regression analysis was performed to identify variables that contributed to BMD. 25-OH-vitamin D status of PD patients was compared with 802 controls (mean age 63.3 years, 50 % men) using linear regression analysis. Osteoporosis (11.8 %) and osteopenia (41.4 %) were common in PD patients. Mean Z-score for the hip was 0.24 (SD 0.93), and for the lumbar spine 0.72 (SD 1.91). Female gender, low weight, and low 25-OH-vitamin D were significantly correlated with BMD of the hip and lumbar spine. PD patients had lower 25(OH)D serum levels than controls (B = -10, p = 0.000). More than half of the patients with early stage PD had an abnormal BMD. Female gender, low weight, and low vitamin D concentration were associated with bone loss. Furthermore, vitamin D concentrations were reduced in PD patients. These results underscore the importance of proactive screening for bone loss and vitamin D deficiency, even in early stages of PD.

  18. Taliglucerase alfa leads to favorable bone marrow responses in patients with type I Gaucher disease.

    PubMed

    van Dussen, L; Zimran, A; Akkerman, E M; Aerts, J M F G; Petakov, M; Elstein, D; Rosenbaum, H; Aviezer, D; Brill-Almon, E; Chertkoff, R; Maas, M; Hollak, C E M

    2013-03-01

    Taliglucerase alfa (Protalix Biotherapeutics, Israel) is a carrot-cell-expressed recombinant human beta-glucocerebrosidase recently approved in the United States for the treatment of type 1 Gaucher disease (GD). As bone disease is one of the most debilitating features of GD, quantification of bone marrow involvement is important for monitoring the response to treatment. Therefore, bone marrow fat fraction (Ff) measured by quantitative chemical shift imaging (QCSI) was included as exploratory parameter to evaluate bone marrow response in treatment naïve GD patients participating in a double-blind, randomized phase III study. Eight GD patients with intact spleens were treated with 30 or 60U/kg biweekly. Ff results were compared to outcomes in 15 untreated Dutch GD patients with a follow-up interval of 1year. Five taliglucerase alfa treated patients had a Ff below the threshold that relates to complication risk (<0.23) at baseline (median (n=8) 0.19, range 0.11-0.35). Ff significantly increased compared to baseline (p=0.012) and compared to untreated patients (p=0.005), already after 1year of follow-up with further improvement up to 36months. In four patients with the lowest Ff, the higher dose resulted in increases above 0.23 within 1year. All patients had sustained improvements in all other parameters. There was no influence of antibodies on response parameters. Treatment with taliglucerase alfa results in significant increases in lumbar spine fat fractions, which indicates clearance of Gaucher cells from the bone marrow.

  19. The KISS1 Receptor as an In Vivo Microenvironment Imaging Biomarker of Multiple Myeloma Bone Disease

    PubMed Central

    Brandl, Andreas; Müller, Marc; Hofbauer, Lorenz C.; Beilhack, Andreas; Ebert, Regina; Glüer, Claus C.; Tiwari, Sanjay; Schütze, Norbert; Jakob, Franz

    2016-01-01

    Multiple myeloma is one of the most common hematological diseases and is characterized by an aberrant proliferation of plasma cells within the bone marrow. As a result of crosstalk between cancer cells and the bone microenvironment, bone homeostasis is disrupted leading to osteolytic lesions and poor prognosis. Current diagnostic strategies for myeloma typically rely on detection of excess monoclonal immunoglobulins or light chains in the urine or serum. However, these strategies fail to localize the sites of malignancies. In this study we sought to identify novel biomarkers of myeloma bone disease which could target the malignant cells and/or the surrounding cells of the tumor microenvironment. From these studies, the KISS1 receptor (KISS1R), a G-protein-coupled receptor known to play a role in the regulation of endocrine functions, was identified as a target gene that was upregulated on mesenchymal stem cells (MSCs) and osteoprogenitor cells (OPCs) when co-cultured with myeloma cells. To determine the potential of this receptor as a biomarker, in vitro and in vivo studies were performed with the KISS1R ligand, kisspeptin, conjugated with a fluorescent dye. In vitro microscopy showed binding of fluorescently-labeled kisspeptin to both myeloma cells as well as MSCs under direct co-culture conditions. Next, conjugated kisspeptin was injected into immune-competent mice containing myeloma bone lesions. Tumor-burdened limbs showed increased peak fluorescence compared to contralateral controls. These data suggest the utility of the KISS1R as a novel biomarker for multiple myeloma, capable of targeting both tumor cells and host cells of the tumor microenvironment. PMID:27158817

  20. Bone scan findings in Kienböck's disease. A case report with atypical findings and literature review.

    PubMed

    Stuckey, S L; Kalff, V; Hoy, G

    1997-07-01

    The authors present an 18-year-old man who had a 5-month history of a painful left wrist. Despite the prolonged history, discrete photopenia on the blood-pool phase and photopenia relative to the remainder of the ipsilateral carpus on the delayed phase of a bone scan in the region of the lunate was shown. When Kienböck's disease is seen in its late phase, the bone scan findings may be atypical in that they may not show the usual three-phase bone scintigraphic evidence of bone remodeling expected in delayed diagnosis avascular necrosis. A review of the previous literature is presented.

  1. A pilot study on the impact of body composition on bone and mineral metabolism in Parkinson's disease.

    PubMed

    Fernández, María C; Parisi, Muriel S; Díaz, Sergio P; Mastaglia, Silvina R; Deferrari, Juan M; Seijo, Mariana; Bagur, Alicia; Micheli, Federico; Oliveri, Beatriz

    2007-08-01

    The impact of body composition on bone and mineral metabolism in Parkinson's disease (PD) was evaluated. Body fat mass, lean mass, bone mineral content, and bone mineral density (BMD) were measured by DXA in 22 PD patients and 104 controls. Female patients exhibited reduced body mass index, fat mass, and BMD compared to controls (p<0.05). Significant positive correlation was found between 25 OHD levels and BMC. Diminished bone mass in women with PD was found to be associated with alterations in body composition and low 25 OHD levels.

  2. Role of exopolysaccharide in Aggregatibacter actinomycetemcomitans-induced bone resorption in a rat model for periodontal disease.

    PubMed

    Shanmugam, Mayilvahanan; Gopal, Prerna; El Abbar, Faiha; Schreiner, Helen C; Kaplan, Jeffrey B; Fine, Daniel H; Ramasubbu, Narayanan

    2015-01-01

    Aggregatibacter actinomycetemcomitans a causative agent of periodontal disease in humans, forms biofilm on biotic and abiotic surfaces. A. actinomycetemcomitans biofilm is heterogeneous in nature and is composed of proteins, extracellular DNA and exopolysaccharide. To explore the role played by the exopolysaccharide in the colonization and disease progression, we employed genetic reduction approach using our rat model of A. actinomycetemcomitans-induced periodontitis. To this end, a genetically modified strain of A. actinomycetemcomitans lacking the pga operon was compared with the wild-type strain in the rat infection model. The parent and mutant strains were primarily evaluated for bone resorption and disease. Our study showed that colonization, bone resorption/disease and antibody response were all elevated in the wild-type fed rats. The bone resorption/disease caused by the pga mutant strain, lacking the exopolysaccharide, was significantly less (P < 0.05) than the bone resorption/disease caused by the wild-type strain. Further analysis of the expression levels of selected virulence genes through RT-PCR showed that the decrease in colonization, bone resorption and antibody titer in the absence of the exopolysaccharide might be due to attenuated levels of colonization genes, flp-1, apiA and aae in the mutant strain. This study demonstrates that the effect exerted by the exopolysaccharide in A. actinomycetemcomitans-induced bone resorption has hitherto not been recognized and underscores the role played by the exopolysaccharide in A. actinomycetemcomitans-induced disease.

  3. A fresh look at metabolic bone diseases in reptiles and amphibians.

    PubMed

    Klaphake, Eric

    2010-09-01

    Metabolic bone diseases (MBDs) are a common presenting complaint in reptiles and amphibians to veterinarians; however, understanding of the causes and diagnostic and treatment options is often extrapolated from human or other mammalian medicine models. Although the roles of UV-B, calcium, phosphorus, and cholecalciferol are better understood in some MBDs, there remain many X factors that are not. Likewise, quantitative diagnosis of MBDs has been difficult not only in terms of staging a disease but also regarding whether or not a condition is present. Treatment options also present challenges in corrective husbandry and diet modifications, medication/modality selection, and dosing/regimen parameters.

  4. [Updates on Lifestyle-Related Diseases and Bone Metabolism. CKD-related osteoporosis].

    PubMed

    Yamada, Shinsuke; Inaba, Masaaki

    2014-11-01

    Chronic kidney disease (CKD) has a high mortality rate of cardiovascular disease (CVD) . As CKD-mineral and bone disorder (CKD-MBD) is the one of the major risk factors in CVD, it is necessary that CKD patients are controlled CKD-MBD appropriately as early as possible. However, it is difficulty that CKD-MBD condition is exactly diagnosed and controlled, because it presents various conditions according to the difference of patient's background such as having diabetes or stage of CKD. We will give an outline of the mechanism in CKD-MBD according to patient's condition and the association between CKD-MBD and vascular calcification.

  5. Differential expression of cartilage and bone-related proteins in pediatric and adult diseased aortic valves.

    PubMed

    Wirrig, Elaine E; Hinton, Robert B; Yutzey, Katherine E

    2011-03-01

    Approximately 5 million people are affected with aortic valve disease (AoVD) in the United States. The most common treatment is aortic valve (AoV) replacement surgery, however, replacement valves are susceptible to failure, necessitating additional surgeries. The molecular mechanisms underlying disease progression and late AoV calcification are not well understood. Recent studies suggest that genes involved in bone and cartilage development play an active role in osteogenic-like calcification in human calcific AoVD (CAVD). In an effort to define the molecular pathways involved in AoVD progression and calcification, expression of markers of valve mesenchymal progenitors, chondrogenic precursors, and osteogenic differentiation was compared in pediatric non-calcified and adult calcified AoV specimens. Valvular interstitial cell (VIC) activation, extracellular matrix (ECM) disorganization, and markers of valve mesenchymal and skeletal chondrogenic progenitor cells were observed in both pediatric and adult AoVD. However, activated BMP signaling, increased expression of cartilage and bone-type collagens, and increased expression of the osteogenic marker Runx2 are observed in adult diseased AoVs. They are not observed in the majority of pediatric diseased valves, representing a marked distinction in the molecular profile between pediatric and adult diseased AoVs. The combined evidence suggests that an actively regulated osteochondrogenic disease process underlies the pathological changes affecting AoVD progression, ultimately resulting in stenotic AoVD. Both pediatric and adult diseased AoVs express protein markers of valve mesenchymal and chondrogenic progenitor cells while adult diseased AoVs also express proteins involved in osteogenic calcification. These findings provide specific molecular indicators of AoVD progression, which may lead to identification of early disease markers and the development of potential therapeutics.

  6. Erdheim-Chester disease: a case report with pulmonary, kidney involvement and bone lesions.

    PubMed

    Mounach, Aziza; Nouijai, Abderrzak; Achemlal, Lahsen; El Maghraoui, Abdellah; Bezza, Ahmed

    2010-03-01

    We report the case of a 42-year-old woman who was admitted in 2002 for exploration of diffuse bone pain. She had medical history of pulmonary tuberculosis. Her current symptoms had started 9 months earlier and consisted of bone pain, affecting the legs. She had asthenia and weight loss. At admission, physical examination showed bilateral and symmetrical long bone pain, especially the knees and the ankles. Physical exam was normal elsewhere. Laboratory tests showed inflammation, with an erythrocyte sedimentation rate of 90 mm/h and C-reactive protein 8 mg/l. Protein electrophoresis, red and white blood cell count, renal, and liver function tests were normal. Serum calcium, phosphorus, and urinary calcium were normal. Radiographs showed multiple mixed bone lesions with sclerotic and lytic areas of the femora, tibiae, humerus. Chest radiographs and thoracic computed tomography (CT) scan showed pulmonary fibrosis. Biopsy of the tibial area displayed foamy lipid-laden histiocytes, confirming the diagnosis of Erdheim-Chester disease. Patient was treated with prednisolone plus cyclophosphamide. Her clinical condition improved remarkably during 4 years, but she developed acute renal failure leading to death.

  7. Role of odanacatib in reducing bone loss due to endodontic disease: An overview

    PubMed Central

    Bahuguna, Rachana; Jain, Atul; Khan, Suleman Abbas; Arvind, M. S.

    2016-01-01

    Aims and Objectives: Through a comprehensive literature review, this article provides an overview of the potential role of odanacatib (ODN) in reducing bone loss due to endodontic disease. Materials and Methods: A literature review was performed in PubMed Central, MEDLINE, Cochrane Library, and EBSCO databases. The articles identified included those published between 2002 and 2016. Based on the predetermined inclusion and exclusion criteria, out of 237 articles found, 50 were selected for this review. Results: Cathepsin K (CstK), which is indispensible to the immune system, also plays an important role in osteoclastic bone resorption. ODN, which is an orally active, selective, and effective inhibitor of CstK, decreases bone resorption by selectively inhibiting proteolysis of matrix proteins by CstK, without affecting other osteoclastic activity or osteoblast viability. Conclusion: The goal of endodontic treatment is to achieve a clinically asymptomatic state along with formation of reparative bone. This process could take 6 months or longer, hence, an earlier reversal of the resorption process could lead to faster healing and resolution of the periapical lesion. Use of ODN can be of help in achieving this goal. PMID:28217533

  8. Leptin in chronic kidney disease: a link between hematopoiesis, bone metabolism, and nutrition.

    PubMed

    Zhang, Jingjing; Wang, Ningning

    2014-06-01

    Anemia, dyslipidemia, malnutrition, together with mineral and bone disorders are common complications in patients with chronic kidney disease (CKD). All are associated with increased risk of mortality. Leptin is a small peptide hormone that is mainly but not exclusively produced in adipose tissue. It is also secreted by normal human osteoblasts, subchondral osteoblasts, placental syncytiotrophoblasts, and the gastric epithelium. Leptin binds to its receptors in the hypothalamus to regulate bone metabolism and food intake. Leptin also has several other important metabolic effects on peripheral tissues, including the liver, skeletal muscle, and bone marrow. Leptin is cleared principally by the kidney. Not surprisingly, serum leptin appears to increase concurrently with declines in the glomerular filtration rate in patients with CKD. A growing body of evidence suggests that leptin might be closely related to hematopoiesis, nutrition, and bone metabolism in CKD patients. Results are conflicting regarding leptin in patients with CKD, in whom both beneficial and detrimental effects on uremia outcome are found. This review elucidates the discovery of leptin and its receptors, changes in serum or plasma leptin levels, the functions of leptin, relationships between leptin and the complications mentioned above, and pharmaceutical interventions in serum leptin levels in patients with CKD.

  9. ZNF687 Mutations in Severe Paget Disease of Bone Associated with Giant Cell Tumor

    PubMed Central

    Divisato, Giuseppina; Formicola, Daniela; Esposito, Teresa; Merlotti, Daniela; Pazzaglia, Laura; Del Fattore, Andrea; Siris, Ethel; Orcel, Philippe; Brown, Jacques P.; Nuti, Ranuccio; Strazzullo, Pasquale; Benassi, Maria Serena; Cancela, M. Leonor; Michou, Laetitia; Rendina, Domenico; Gennari, Luigi; Gianfrancesco, Fernando

    2016-01-01

    Paget disease of bone (PDB) is a skeletal disorder characterized by focal abnormalities of bone remodeling, which result in enlarged and deformed bones in one or more regions of the skeleton. In some cases, the pagetic tissue undergoes neoplastic transformation, resulting in osteosarcoma and, less frequently, in giant cell tumor of bone (GCT). We performed whole-exome sequencing in a large family with 14 PDB-affected members, four of whom developed GCT at multiple pagetic skeletal sites, and we identified the c.2810C>G (p.Pro937Arg) missense mutation in the zinc finger protein 687 gene (ZNF687). The mutation precisely co-segregated with the clinical phenotype in all affected family members. The sequencing of seven unrelated individuals with GCT associated with PDB (GCT/PDB) identified the same mutation in all individuals, unravelling a founder effect. ZNF687 is highly expressed during osteoclastogenesis and osteoblastogenesis and is dramatically upregulated in the tumor tissue of individuals with GCT/PDB. Interestingly, our preliminary findings showed that ZNF687, indicated as a target gene of the NFkB transcription factor by ChIP-seq analysis, is also upregulated in the peripheral blood of PDB-affected individuals with (n = 5) or without (n = 6) mutations in SQSTM1, encouraging additional studies to investigate its potential role as a biomarker of PDB risk. PMID:26849110

  10. PSMA-PET/CT-Positive Paget Disease in a Patient with Newly Diagnosed Prostate Cancer: Imaging and Bone Biopsy Findings.

    PubMed

    Froehner, Michael; Toma, Marieta; Zöphel, Klaus; Novotny, Vladimir; Laniado, Michael; Wirth, Manfred P

    2017-01-01

    A 67-year-old man diagnosed with Gleason score 4 + 5 = 9 clinically localized prostate cancer with (68)Ga-labeled prostate-specific membrane antigen-targeted ligand positron emission tomography/computed tomography (PSMA-PET/CT) positive Paget bone disease is described. Immunohistochemical staining revealed weak PSMA positivity of the bone lesion supporting the hypothesis that neovasculature might explain positive PSMA-PET/CT findings in Paget disease.

  11. PSMA-PET/CT-Positive Paget Disease in a Patient with Newly Diagnosed Prostate Cancer: Imaging and Bone Biopsy Findings

    PubMed Central

    Toma, Marieta; Zöphel, Klaus; Novotny, Vladimir; Laniado, Michael

    2017-01-01

    A 67-year-old man diagnosed with Gleason score 4 + 5 = 9 clinically localized prostate cancer with 68Ga-labeled prostate-specific membrane antigen-targeted ligand positron emission tomography/computed tomography (PSMA-PET/CT) positive Paget bone disease is described. Immunohistochemical staining revealed weak PSMA positivity of the bone lesion supporting the hypothesis that neovasculature might explain positive PSMA-PET/CT findings in Paget disease.

  12. Co-registration of multi-modality imaging allows for comprehensive analysis of tumor-induced bone disease

    PubMed Central

    Seeley, Erin H.; Wilson, Kevin J.; Yankeelov, Thomas E.; Johnson, Rachelle W.; Gore, John C.; Caprioli, Richard M.; Matrisian, Lynn M.; Sterling, Julie A.

    2014-01-01

    Bone metastases are a clinically significant problem that arises in approximately 70% of metastatic breast cancer patients. Once established in bone, tumor cells induce changes in the bone microenvironment that lead to bone destruction, pain, and significant morbidity. While much is known about the later stages of bone disease, less is known about the earlier stages or the changes in protein expression in the tumor micro-environment. Due to promising results of combining magnetic resonance imaging (MRI) and Matrix-Assisted Laser Desorption/Ionization Imaging Mass Spectrometry (MALDI IMS) ion images in the brain, we developed methods for applying these modalities to models of tumor-induced bone disease in order to better understand the changes in protein expression that occur within the tumor-bone microenvironment. Specifically, we integrated three dimensional-volume reconstructions of spatially resolved MALDI IMS with high-resolution anatomical and diffusion weighted MRI data and histology in an intratibial model of breast tumor-induced bone disease. This approach enables us to analyze proteomic profiles from MALDI IMS data with corresponding in vivo imaging and ex vivo histology data. To the best of our knowledge, this is the first time these three modalities have been rigorously registered in the bone. The MALDI mass-to-charge ratio peaks indicate differential expression of calcyclin, ubiquitin, and other proteins within the tumor cells, while peaks corresponding to hemoglobin A and calgranulin A provided molecular information that aided in the identification of areas rich in red and white blood cells, respectively. This multimodality approach will allow us to comprehensively understand the bone-tumor microenvironment and thus may allow us to better develop and test approaches for inhibiting bone metastases. PMID:24487126

  13. Notch pathway inhibition controls myeloma bone disease in the murine MOPC315.BM model

    PubMed Central

    Schwarzer, R; Nickel, N; Godau, J; Willie, B M; Duda, G N; Schwarzer, R; Cirovic, B; Leutz, A; Manz, R; Bogen, B; Dörken, B; Jundt, F

    2014-01-01

    Despite evidence that deregulated Notch signalling is a master regulator of multiple myeloma (MM) pathogenesis, its contribution to myeloma bone disease remains to be resolved. Notch promotes survival of human MM cells and triggers human osteoclast activity in vitro. Here, we show that inhibition of Notch through the γ-secretase inhibitor XII (GSI XII) induces apoptosis of murine MOPC315.BM myeloma cells with high Notch activity. GSI XII impairs murine osteoclast differentiation of receptor activator of NF-κB ligand (RANKL)-stimulated RAW264.7 cells in vitro. In the murine MOPC315.BM myeloma model GSI XII has potent anti-MM activity and reduces osteolytic lesions as evidenced by diminished myeloma-specific monoclonal immunoglobulin (Ig)-A serum levels and quantitative assessment of bone structure changes via high-resolution microcomputed tomography scans. Thus, we suggest that Notch inhibition through GSI XII controls myeloma bone disease mainly by targeting Notch in MM cells and possibly in osteoclasts in their microenvironment. We conclude that Notch inhibition is a valid therapeutic strategy in MM. PMID:24927406

  14. Notch pathway inhibition controls myeloma bone disease in the murine MOPC315.BM model.

    PubMed

    Schwarzer, R; Nickel, N; Godau, J; Willie, B M; Duda, G N; Schwarzer, R; Cirovic, B; Leutz, A; Manz, R; Bogen, B; Dörken, B; Jundt, F

    2014-06-13

    Despite evidence that deregulated Notch signalling is a master regulator of multiple myeloma (MM) pathogenesis, its contribution to myeloma bone disease remains to be resolved. Notch promotes survival of human MM cells and triggers human osteoclast activity in vitro. Here, we show that inhibition of Notch through the γ-secretase inhibitor XII (GSI XII) induces apoptosis of murine MOPC315.BM myeloma cells with high Notch activity. GSI XII impairs murine osteoclast differentiation of receptor activator of NF-κB ligand (RANKL)-stimulated RAW264.7 cells in vitro. In the murine MOPC315.BM myeloma model GSI XII has potent anti-MM activity and reduces osteolytic lesions as evidenced by diminished myeloma-specific monoclonal immunoglobulin (Ig)-A serum levels and quantitative assessment of bone structure changes via high-resolution microcomputed tomography scans. Thus, we suggest that Notch inhibition through GSI XII controls myeloma bone disease mainly by targeting Notch in MM cells and possibly in osteoclasts in their microenvironment. We conclude that Notch inhibition is a valid therapeutic strategy in MM.

  15. From bone abnormalities to mineral metabolism dysregulation in autosomal dominant polycystic kidney disease.

    PubMed

    Mekahli, Djalila; Bacchetta, Justine

    2013-11-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic cause of kidney failure. It is a systemic disorder, not only affecting the kidneys, but also associated with cyst formation in other organs such as the liver, spleen, pancreas, and seminal vesicles. Other extra-renal symptoms may consist of intracranial arterial aneurysms, cardiac valvular defects, abdominal and inguinal hernias and colonic diverticulosis. Very little is known regarding bone involvement in ADPKD; however, recent evidence has revealed the potential role of fibroblast growth factor 23 (FGF23). FGF23 is an endocrine fibroblast growth factor acting in the kidney as a phosphaturic hormone and a suppressor of active vitamin D with key effects on the bone/kidney/parathyroid axis, and has been shown to increase in patients with ADPKD, even with normal renal function. The aim of this review is to provide an overview of bone and mineral abnormalities found in experimental models and in patients with ADPKD, and to discuss the possible role of FGF23 in this disease.

  16. Clinical Outcomes of Radial Shortening Osteotomy and Vascularized Bone Graft in Kienböck's Disease.

    PubMed

    Dehghani, Mohammad; Moshgelani, Mohammad Ali; Nouraei, Mohammad Hadi; Dehghani, Shaghayegh; Gholshahi, Maryam

    2014-01-01

    The aim of this study was to compare two surgery methods including radial shortening and radial shortening combined with vascularized bone graft for treatment of stage II or IIIa of Kienböck's disease. It is a randomized, controlled clinical trial, which was carried out in 2011-2013. Twenty-four patients were assigned equally to radial shortening group (A) or radial shortening combined with vascularized bone graft group (B). The outcome was assessed by Mayo Wrist score before and 9 months after surgery. The mean Mayo Wrist score (SD) was 27.1 (15.4) and 32.5 (18.3) before surgery and 74.6 (5.4) and 85.8 (5.1) after surgery for groups A and B, respectively. The mean score increased in both groups, and it was higher in group B significantly. Radial shortening combined with vascularized bone graft is a valuable method which can be more effective than radial shortening alone, in early stages of Kienböck's disease. This trial is registered with IRCT201404127841N5.

  17. [Italian guidelines for the diagnosis and treatment of Paget's disease of bone].

    PubMed

    Adami, S; Bartolozzi, P; Brandi, M L; Falchetti, A; Filipponi, P; Gonnelli, S; Bianchi, G; Isaia, G C; Nuti, R

    2007-01-01

    Paget's disease of bone is a chronic focal abnormality of bone turnover that remains totally asymptomatic over a very long period of time but that eventually ensue in bone pain and skeletal deformities. Although, in the last decade new insights have been obtained on its etiology, this remains largely obscure. Effective medical treatment (based on the use of bisphosphonates) has become available and the diagnostic procedures are now well defined. However, there remains considerable controversy regarding the hierarchy of diagnostic procedures and the medical treatment threshold. In the last few years different institution have published national guidelines, reflecting local national health systems and the available medical treatment. In this review, a working group derived from members of the SIOMMMS has examined the information available regarding the diagnosis and treatment of Paget's disease in order to develop guidelines to assist in the management of this condition. The first draft was then extensively reviewed by experts derived from the most representative scientific societies of rheumatology, internal medicine, and orthopaedic surgery. The document provides the most updated recommendations based primarily on the "evidence-based- medicine" but also on the Italian regulation for the diagnostic procedures and on the available medical treatments.

  18. Clinical Outcomes of Radial Shortening Osteotomy and Vascularized Bone Graft in Kienböck's Disease

    PubMed Central

    Dehghani, Mohammad; Nouraei, Mohammad Hadi; Dehghani, Shaghayegh; Gholshahi, Maryam

    2014-01-01

    The aim of this study was to compare two surgery methods including radial shortening and radial shortening combined with vascularized bone graft for treatment of stage II or IIIa of Kienböck's disease. It is a randomized, controlled clinical trial, which was carried out in 2011–2013. Twenty-four patients were assigned equally to radial shortening group (A) or radial shortening combined with vascularized bone graft group (B). The outcome was assessed by Mayo Wrist score before and 9 months after surgery. The mean Mayo Wrist score (SD) was 27.1 (15.4) and 32.5 (18.3) before surgery and 74.6 (5.4) and 85.8 (5.1) after surgery for groups A and B, respectively. The mean score increased in both groups, and it was higher in group B significantly. Radial shortening combined with vascularized bone graft is a valuable method which can be more effective than radial shortening alone, in early stages of Kienböck's disease. This trial is registered with IRCT201404127841N5. PMID:27382615

  19. Lesions in the thymus and bone marrow in chicks with experimentally induced chicken infectious anemia disease

    PubMed Central

    Kuscu, Burak

    2008-01-01

    One-day-old SPF chicks were inoculated with the Cux-l strain of chicken infectious anemia virus (CIAV), and the clinical development of disease and its macroscopic and microscopic alterations in the thymus and bone marrow, were observed. Tissue sections of thymus and bone marrow were stained using the streptavidin-biotin peroxidase method and examined under light microscope for evaluation of antigenic intensities in tissues. Those findings were then compared with blood parameters and ELISA results obtained through collected sera during sacrifice procedures. We sought to determine: the localization of viral antigens in thymus and bone marrow tissues after inoculation, the correlation between antigen intensities and hematologic, serologic and histopathologic findings, definitive diagnostic criteria using histopathologic and immunoperoxidase methods, and the reliability of these methods in the diagnosis of CIAV infection. For this purpose, 83, one-day-old SPF chicks were used. The birds were divided into experimental (n = 52) and control (n = 26) groups. A virus dose of TCID50 of 100,000/ml was administered intramuscularly to every bird in the experimental group. Based on the results of this study, we have suggested that clinical examination, along with macroscopic and microscopic evaluation of the thymus and bone marrow, maybe undertaken starting from day 7 post-inoculation (PI). ELISA, might be of value, as it might give consistent results starting from day 14 PI. However, the most reliable results were obtained through examination of thymus and bone marrow sections from infected birds stained by immunoperoxidase technique, as early as day 4 PI. PMID:18296884

  20. Fracture in compression of brittle solids

    NASA Technical Reports Server (NTRS)

    1983-01-01

    The fracture of brittle solids in monotonic compression is reviewed from both the mechanistic and phenomenological points of view. The fundamental theoretical developments based on the extension of pre-existing cracks in general multiaxial stress fields are recognized as explaining extrinsic behavior where a single crack is responsible for the final failure. In contrast, shear faulting in compression is recognized to be the result of an evolutionary localization process involving en echelon action of cracks and is termed intrinsic.

  1. Micromechanics of brittle creep in rocks

    NASA Astrophysics Data System (ADS)

    Brantut, N.; Baud, P.; Heap, M. J.; Meredith, P. G.

    2012-08-01

    In the upper crust, the chemical influence of pore water promotes time dependent brittle deformation through sub-critical crack growth. Sub-critical crack growth allows rocks to deform and fail at stresses well below their short-term failure strength, and even at constant applied stress (“brittle creep”). Here we provide a micromechanical model describing time dependent brittle creep of water-saturated rocks under triaxial stress conditions. Macroscopic brittle creep is modeled on the basis of microcrack extension under compressive stresses due to sub-critical crack growth. The incremental strains due to the growth of cracks in compression are derived from the sliding wing crack model of Ashby and Sammis (1990), and the crack length evolution is computed from Charles' law. The macroscopic strains and strain rates computed from the model are non linear, and compare well with experimental results obtained on granite, low porosity sandstone and basalt rock samples. Primary creep (decelerating strain) corresponds to decelerating crack growth, due to an initial decrease in stress intensity factor with increasing crack length in compression. Tertiary creep (accelerating strain as failure is approached) corresponds to an increase in crack growth rate due to crack interactions. Secondary creep with apparently constant strain rate arises as an inflexion between those two end-member phases. The minimum strain rate at the inflexion point can be estimated analytically as a function of model parameters, effective confining pressure and temperature, which provides an approximate creep law for the process. The creep law is used to infer the long term strain rate as a function of depth in the upper crust due to the action of the applied stresses: in this way, sub-critical cracking reduces the failure stress in a manner equivalent to a decrease in cohesion. We also investigate the competition with pressure solution in porous rocks, and show that the transition from sub

  2. Healing of fracturing-bone disease occurring in patients on dialysis. A prospective study.

    PubMed

    Milne, F J; Hudson, G A; Meyers, A M; Baily, P; Barmeir, E; Dubowitz, B; Reis, P

    1982-06-19

    Ten patients developed fracturing-bone disease (osteomalacia) while on dialysis against water with high levels of aluminium. Eight patients remained on dialysis, using de-ionized or reverse-osmosis water, and 2 received a renal transplant. Clinical improvement as regards bone pain and proximal muscle weakness occurred in 6 months and radiographic evidence of healing of the pseudofractures was seen at approximately 12 months. Associated osteopenia and hyperparathyroidism were found in most patients, but no significant change in either was noted during the study period. The serum parathyroid hormone levels rose significantly in the patients who remained on dialysis. The chest and pelvic deformities typical of healed osteomalacia were seen. This dramatic improvement can only be attributed to the removal of some water-borne element, either by changing the water used in the dialysis or by successful renal transplantation. Aluminium-containing phosphate binders were used throughout the study in the patients on dialysis, and hypophosphataemia was never a feature.

  3. The chronic kidney disease - Mineral bone disorder (CKD-MBD): Advances in pathophysiology.

    PubMed

    Hruska, Keith A; Sugatani, Toshifumi; Agapova, Olga; Fang, Yifu

    2017-01-21

    The causes of excess cardiovascular mortality associated with chronic kidney disease (CKD) have been attributed in part to the CKD-mineral bone disorder syndrome (CKD-MBD), wherein, novel cardiovascular risk factors have been identified. New advances in the causes of the CKD-MBD are discussed in this review. They demonstrate that repair and disease processes in the kidneys release factors to the circulation that cause the systemic complications of CKD. The discovery of WNT inhibitors, especially Dickkopf 1 (Dkk1), produced during renal repair as participating in the pathogenesis of the vascular and skeletal components of the CKD-MBD implied that additional pathogenic factors are critical. This lead to the discovery that activin A is a second renal repair factor circulating in increased levels during CKD. Activin A derives from peritubular myofibroblasts of diseased kidneys, wherein it stimulates fibrosis, and decreases tubular klotho expression. Activin A binds to the type 2 activin A receptor, ActRIIA, which is variably affected by CKD in the vasculature. In diabetic/atherosclerotic aortas, specifically in vascular smooth muscle cells (VSMC), ActRIIA signaling is inhibited and contributes to CKD induced VSMC dedifferentiation, osteogenic transition and neointimal atherosclerotic calcification. In nondiabetic/nonatherosclerotic aortas, CKD increases VSMC ActRIIA signaling, and vascular fibroblast signaling causing the latter to undergo osteogenic transition and stimulate vascular calcification. In both vascular situations, a ligand trap for ActRIIA prevented vascular calcification. In the skeleton, activin A is responsible for CKD stimulation of osteoclastogenesis and bone remodeling increasing bone turnover. These studies demonstrate that circulating renal repair and injury factors are causal of the CKD-MBD and CKD associated cardiovascular disease.

  4. Fabrication of brittle materials -- current status

    SciTech Connect

    Scattergood, R.O.

    1988-12-01

    The research initiatives in the area of precision fabrication will be continued in the upcoming year. Three students, T. Bifano (PhD), P. Blake (PhD) and E. Smith (MS), finished their research programs in the last year. Sections 13 and 14 will summarize the essential results from the work of the Materials Engineering students Blake and Smith. Further details will be presented in forthcoming publications that are now in preparation. The results from Bifano`s thesis have been published in adequate detail and need not be summarized further. Three new students, S. Blackley (MS), H. Paul (PhD), and S. Smith (PhD) have joined the program and will continue the research efforts in precision fabrication. The programs for these students will be outlined in Sections 15 and 16. Because of the success of the earlier work in establishing new process models and experimental techniques for the study of diamond turning and diamond grinding, the new programs will, in part, build upon the earlier work. This is especially true for investigations concerned with brittle materials. The basic understanding of material response of nominally brittle materials during machining or grinding operations remains as a challenge. The precision fabrication of brittle materials will continue as an area of emphasis for the Precision Engineering Center.

  5. CYR61/CCN1 stimulates proliferation and differentiation of osteoblasts in vitro and contributes to bone remodeling in vivo in myeloma bone disease.

    PubMed

    Liu, Hui; Peng, Fengping; Liu, Zhaoyun; Jiang, Fengjuan; Li, Lijuan; Gao, Shan; Wang, Guojin; Song, Jia; Ruan, Erbao; Shao, Zonghong; Fu, Rong

    2017-02-01

    Cysteine-rich 61 (CYR61/CCN1), a secreted protein in bone marrow (BM) microenvironment, has diverse effects on many cellular activities such as growth and differentiation. However, the effect of CCN1 on osteoblasts (OBs) in myeloma bone disease remains unclear. In our study, the level of CCN1 in multiple myeloma (MM) patients was detected by ELISA and RT-PCR. The proliferation and differentiation of OBs from MM patients were observed after stimulated by CCN1 in vitro. The myeloma cells transduced with CYR61 gene (RPMI‑8226/CYR61) were injected in a mouse model to evaluate the efficacy of CCN1 in vivo and compare with zoledronic acid. The results showed that CYR61/CCN1 levels in BM supernatant and OBs both elevated significantly in all newly diagnosed MM patients, especially in patients without bone disease (P=0.001 and P<0.001). After 30 ng/l CCN1 stimulation for 24 h, the quantity and mineralization of OBs increased significantly in vitro (P=0.046 and 0.048). The transcription factors of Wnt pathway, runt-related transcription factor 2 (Runx2) and β-catenin were upregulated in OBs after CCN1 stimulation (P=0.012 and 0.011). After injection of RPMI‑8226 cells, bone lesions were observed obviously by microCT and histochemistry at 7 weeks. Radiographic analysis of the bones showed decreased resorption in CCN1 overexpression group and zoledronic acid group, while severe resorption in negative control. Furthermore, trabecular bone volume in CCN1 overexpression group (1.7539±0.16949) was significantly higher than zoledronic acid group (1.2839±0.077) (P=0.012). In conclusion, CCN1 can stimulate the proliferation and differentiation of OBs in vitro and contribute to bone remodeling in vivo in MBD.

  6. Overexpression of RANKL in osteoblasts: a possible mechanism of susceptibility to bone disease in cystic fibrosis.

    PubMed

    Delion, Martial; Braux, Julien; Jourdain, Marie-Laure; Guillaume, Christine; Bour, Camille; Gangloff, Sophie; Pimpec-Barthes, Françoise Le; Sermet-Gaudelus, Isabelle; Jacquot, Jacky; Velard, Frédéric

    2016-09-01

    Bone fragility and loss are a significant cause of morbidity in patients with cystic fibrosis (CF), and the lack of effective therapeutic options means that treatment is more often palliative rather than curative. A deeper understanding of the pathogenesis of CF-related bone disease (CFBD) is necessary to develop new therapies. Defective CF transmembrane conductance regulator (CFTR) protein and chronic inflammation in bone are important components of the CFBD development. The receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) drive the regulation of bone turnover. To investigate their roles in CFBD, we evaluated the involvement of defective CFTR in their production level in CF primary human osteoblasts with and without inflammatory stimulation, in the presence or not of pharmacological correctors of the CFTR. No major difference in cell ultrastructure was noted between cultured CF and non-CF osteoblasts, but a delayed bone matrix mineralization was observed in CF osteoblasts. Strikingly, resting CF osteoblasts exhibited strong production of RANKL protein, which was highly localized at the cell membrane and was enhanced in TNF (TNF-α) or IL-17-stimulated conditions. Under TNF stimulation, a defective response in OPG production was observed in CF osteoblasts in contrast to the elevated OPG production of non-CF osteoblasts, leading to an elevated RANKL-to-OPG protein ratio in CF osteoblasts. Pharmacological inhibition of CFTR chloride channel conductance in non-CF osteoblasts replicated both the decreased OPG production and the enhanced RANKL-to-OPG ratio. Interestingly, using CFTR correctors such as C18, we significantly reduced the production of RANKL by CF osteoblasts, in both resting and TNF-stimulated conditions. In conclusion, the overexpression of RANKL and high membranous RANKL localization in osteoblasts are related to defective CFTR, and may worsen bone resorption, leading to bone loss in patients with CF. Targeting

  7. New aspects of treatment of renal bone disease in dialysis patients.

    PubMed

    Spasovski, G

    2007-07-01

    The abnormalities in bone and mineral metabolism in chronic kidney disease patients are associated with an increased risk of fractures, vascular calcifications and cardiovascular diseases. A few decades ago hyperphosphatemia and the common development of secondary hyperparathyroidism were thought to be the main problem to deal with. Since dietary phosphate restriction and haemodialysis were not proven to be sufficient measures to reduce phosphorus, phosphate-binding therapy has been widely instituted as a treatment option. Various types of phosphate binders employed over the years have contributed to the changing spectrum of renal osteodystrophy from high to low bone turnover along with the shift from hypocalcemia and negative calcium balance towards hypercalcemia and the positive calcium balance. Thus, hypercalcemia instead of hyperphosphatemia is nowadays associated with the increased risk of vascular calcification, morbidity and mortality in the dialysis population. Besides the very expensive non-calcium based phosphate binders, at least two common tools may be helpful in the treatment of hypercalcemia and adynamic bone. A reduced daily use of calcium carbonate/acetate up to 1g per main meal is an easily manageable and inexpensive tool. The second option for stimulation of parathyroid gland activity and bone turnover is the lowering of the dialysate calcium concentration. In conclusion, an aggressive treatment of hyperphosphatemia and calcium overload might lead towards an opposite effect of hypoparathyroidism and hypercalcemia. Reasonable treatment strategies based on a careful monitoring should be employed in order to prevent related consequences and to contribute to a better long-term quality of life and survival of dialysis patients.

  8. [Updates on Lifestyle-Related Diseases and Bone Metabolism. Effects of sclerostin on bone metabolism in patients with diabetes].

    PubMed

    Yamamoto, Masahiro

    2014-11-01

    Sclerostin, a glycoprotein encoded by SOST gene and secreted from osteocyte, is known as an antagonist for bone formation induced in canonical Wnt/β-catenin signaling pathway by inhibiting receptor complex formation through binding to LDL receptor-related protein 5/6 (LRP 5/6) . From clinical symptoms observed in the patients with a loss-of-function mutation in LRP 6, disorder of that signal transduction pathway is considered as one of candidate molecular mechanism for the simultaneous occurrence of diabetes mellitus and osteoporosis. The serum sclerostin levels of diabetic patients as well as non-diabetic subjects are significantly and positively correlated with bone mineral density, which is the strongest determinant factor especially for diabetic patients. In addition, sclerostin concentrations are associated with prevalent vertebral fractures independent of bone mineral density as well as bone turnover, suggesting that elevated sclerostin levels reflect poor bone quality.

  9. Modifications to nano- and microstructural quality and the effects on mechanical integrity in Paget's disease of bone.

    PubMed

    Zimmermann, Elizabeth A; Köhne, Till; Bale, Hrishikesh A; Panganiban, Brian; Gludovatz, Bernd; Zustin, Joszef; Hahn, Michael; Amling, Michael; Ritchie, Robert O; Busse, Björn

    2015-02-01

    Paget's disease of bone (PDB) is the second most common bone disease mostly developing after 50 years of age at one or more localized skeletal sites; it is associated with severely high bone turnover, bone enlargement, bowing/deformity, cracking, and pain. Here, to specifically address the origins of the deteriorated mechanical integrity, we use a cohort of control and PDB human biopsies to investigate multiscale architectural and compositional modifications to the bone structure (ie, bone quality) and relate these changes to mechanical property measurements to provide further insight into the clinical manifestations (ie, deformities and bowing) and fracture risk caused by PDB. Here, at the level of the collagen and mineral (ie, nanometer-length scale), we find a 19% lower mineral content and lower carbonate-to-phosphate ratio in PDB, which accounts for the 14% lower stiffness and 19% lower hardness promoting plastic deformation in pathological bone. At the microstructural scale, trabecular regions are known to become densified, whereas cortical bone loses its characteristic parallel-aligned osteonal pattern, which is replaced with a mosaic of lamellar and woven bone. Although we find this loss of anisotropic alignment produces a straighter crack path in mechanically-loaded PDB cases, cortical fracture toughness appears to be maintained due to increased plastic deformation. Clearly, the altered quality of the bone structure in PDB affects the mechanical integrity leading to complications such as bowing, deformities, and stable cracks called fissure fractures associated with this disease. Although the lower mineralization and loss of aligned Haversian structures do produce a lower modulus tissue, which is susceptible to deformities, our results indicate that the higher levels of plasticity may compensate for the lost microstructural features and maintain the resistance to crack growth.

  10. Significant bone microarchitecture impairment in premenopausal women with active celiac disease.

    PubMed

    Zanchetta, María Belén; Costa, Florencia; Longobardi, Vanesa; Longarini, Gabriela; Mazure, Roberto Martín; Moreno, María Laura; Vázquez, Horacio; Silveira, Fernando; Niveloni, Sonia; Smecuol, Edgardo; Temprano, María de la Paz; Hwang, Hui Jer; González, Andrea; Mauriño, Eduardo César; Bogado, Cesar; Zanchetta, Jose R; Bai, Julio César

    2015-07-01

    Patients with active celiac disease (CD) are more likely to have osteoporosis and increased risk of fractures. High-resolution peripheral quantitative computed tomography (HR-pQCT) permits three-dimensional exploration of bone microarchitectural characteristics measuring separately cortical and trabecular compartments, and giving a more profound insight into bone disease pathophysiology and fracture. We aimed to determine the volumetric and microarchitectural characteristics of peripheral bones-distal radius and tibia-in an adult premenopausal cohort with active CD assessed at diagnosis. We prospectively enrolled 31 consecutive premenopausal women with newly diagnosed CD (median age 29 years, range: 18-49) and 22 healthy women of similar age (median age 30 years, range 21-41) and body mass index. Compared with controls, peripheral bones of CD patients were significantly lower in terms of total volumetric density mg/cm(3) (mean ± SD: 274.7 ± 51.7 vs. 324.7 ± 45.8, p 0.0006 at the radius; 264.4 ± 48.7 vs. 307 ± 40.7, p 0.002 at the tibia), trabecular density mg/cm(3) (118.6 ± 31.5 vs. 161.9 ± 33.6, p<0.0001 at the radius; 127.9 ± 28.7 vs. 157.6 ± 15.6, p < 0.0001 at the tibia); bone volume/trabecular volume ratio % (9.9 ± 2.6 vs. 13.5 ± 2.8, p<0.0001 at the radius; 10.6 ± 2.4 vs. 13.1 ± 1.3, p < 0.0001 at the tibia); number of trabeculae 1/mm (1.69 ± 0.27 vs. 1.89 ± 0.26, p 0.009 at the radius; 1.53 ± 0.32 vs. 1.80 ± 0.26, p 0.002 at the tibia); and trabecular thickness mm (0.058 ± 0.010 vs. 0.071 ± 0.008, p < 0.0001 at the radius with no significant difference at the tibia). Cortical density was significantly lower in both regions (D comp mg/cm(3) 860 ± 57.2 vs. 893.9 ± 43, p 0.02; 902.7 ± 48.7 vs. 932.6 ± 32.6, p 0.01 in radius and tibia respectively). Although cortical thickness was lower in CD patients, it failed to show any significant inter-group difference (a-8% decay with p 0.11 in both bones). Patients with symptomatic CD (n = 22) had

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

    PubMed

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

    2016-01-01

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

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

    PubMed

    Smink, Jeske J; Leutz, Achim

    2010-03-01

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

  13. Neuropsychological outcomes of several storage diseases with and without bone marrow transplantation.

    PubMed

    Shapiro, E G; Lockman, L A; Balthazor, M; Krivit, W

    1995-01-01

    Neuropsychological assessment is essential in providing documentation of the untreated natural history of storage diseases associated with dementia and quantifying the effectiveness of treatment on central nervous system function. Baseline characterization and outcome of bone marrow transplantation (BMT) for three leukodystrophies and three mucopolysaccharidoses are presented. Results suggests that BMT for Hurler syndrome, adrenoleukodystrophy, and globoid cell leukodystrophy can be effective in preventing dementia if done early enough in the disease. Sanfilippo and Hunter syndromes do not benefit and BMT is not recommended. For metachromatic leukodystrophy, BMT is not recommended for symptomatic early-onset forms of the disease. Further longitudinal follow-up is needed to determine whether the benefits outweigh the risks of BMT for late-onset and preclinical metachromatic leukodystrophy.

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

    PubMed Central

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

    2014-01-01

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

  15. Bone and bone marrow: the same organ.

    PubMed

    Del Fattore, Andrea; Capannolo, Marta; Rucci, Nadia

    2010-11-01

    Interplays between bone and bone marrow are not limited to merely anatomic and histological connections, but include a tight functional correlation. Bone marrow resides within the medullary cavity of the bones and the process of hematopoiesis is regulated, at least in part, by bone cells. Moreover, osteoclasts and osteoblasts derive from precursors of hematopoietic and mesenchymal origin, respectively, both residing within the bone marrow. Alterations in one of these components typically cause impairment in the other, so diseases of the bone marrow compartment often affect the bone and vice versa. All these findings could make us to speculate that bone and bone marrow are not two separate districts, but can be considered as the two elements of the same unique functional unit, the bone-bone marrow organ. Here we will describe histological and functional interplays between bone and bone marrow, and will illustrate some diseases in which this tight correlation is evident.

  16. Low Bone Mass Is a Risk Factor in Periodontal Disease-Related Tooth Loss in Patients with Intellectual Disability

    PubMed Central

    Numoto, Yoko; Mori, Takayuki; Maeda, Shigeru; Tomoyasu, Yumiko; Higuchi, Hitoshi; Egusa, Masahiko; Miyawaki, Takuya

    2013-01-01

    Teeth are fundamental to maintaining good quality of life, but are often lost prematurely in individuals with intellectual disability. Furthermore, since bone mass decreases in menopausal women, women with intellectual disability have an augmented risk of losing their teeth. However, the relationship between periodontal disease-related tooth loss and bone mass has never been studied specifically in patients with intellectual disability. This study evaluated this relationship in a retrospective cohort study. Participants were female dental patients aged between 20 and 50 years and with an intellectual disability, who were treated in the Special Needs Dentistry unit of the Okayama University Hospital from January 2009 to March 2010. Logistic regression analysis was used to analyze which factors affect periodontal disease-related tooth loss. Information relating to 12 predictor variables, including age and bone mass level, was derived from medical records. The 27 subjects had a total of 704 teeth at the time of initial examination, but 20 teeth (2.8%) had been lost owing to periodontal disease by the time bone mass measurements were recorded. Results of the multinomial logistic regression analysis indicated a significant odds ratio for three items: number of missing teeth at the time of initial examination, bone mass, and living environment. This result suggests that low bone mass is an independent risk factor in tooth loss secondary to periodontal disease in patients with intellectual disability. Dentists should thus take account of this heightened risk of tooth loss when caring for post-menopausal women with intellectual disability. PMID:24358063

  17. [Paget's disease of bone and basilar impression associated with an Arnold-Chiari type-1 malformation].

    PubMed

    Iglesias-Osma, C; Gómez Sánchez, J C; Suquia Múgica, B; Querol Prieto, R; de Portugal Alvarez, J

    1997-10-01

    The patient, a 78-year-old female with history of headache and progressive gait disturbance for almost one year, was admitted to our department because of dysphagia and dysphonia since three months before. Neurological examination revealed nystagmus, cerebellar ataxia, deafness, and vesical incontinence. No cerebral injuries were detected by computed tomography (CT) scan, although Paget's. Disease of Bone (PDB) was suggested, confirmed by biochemical and scintigraphic studies. The plain skull X-ray showed platybasia. As all the disarrangements were not explained by PDB complications alone, nuclear magnetic resonance imaging (MRI) was performed which demonstrated an Arnold-Chiari malformation (ACM) type I, with mild tonsillar herniation and anterior compression of the brainstem due to basilar impression, without syringomyelia. The association of PDB and ACM is a peculiarity seldom reported. The surgical approach was rejected, but the severity of symptoms and osteitis deformans biochemical activity needed a treatment; it was orientated to modify bone turnover using etidronate, a bisphosphonate, which induced clinical improvement and a decrease in serum alkaline phosphatase as well as in other bone resorption markers, without side effects. The good status and biochemical remission have been maintained a year later.

  18. Genomic deletion of a long-range bone enhancer misregulatessclerostin in Van Buchem disease

    SciTech Connect

    Loots, Gabriela G.; Kneissel, Michaela; Keller, Hansjoerg; Baptist, Myma; Chang, Jessie; Collette, Nicole M.; Ovcharenko, Dmitriy; Plajzer-Frick, Ingrid; Rubin, Edward M.

    2005-04-15

    Mutations in distant regulatory elements can negatively impact human development and health, yet due to the difficulty of detecting these critical sequences we predominantly focus on coding sequences for diagnostic purposes. We have undertaken a comparative sequence-based approach to characterize a large noncoding region deleted in patients affected by Van Buchem disease (VB), a severe sclerosing bone dysplasia. Using BAC recombination and transgenesis we characterized the expression of human sclerostin (sost) from normal (hSOSTwt) or Van Buchem(hSOSTvb D) alleles. Only the hSOSTwt allele faithfully expressed high levels of human sost in the adult bone and impacted bone metabolism, consistent with the model that the VB noncoding deletion removes a sost specific regulatory element. By exploiting cross-species sequence comparisons with in vitro and in vivo enhancer assays we were able to identify a candidate enhancer element that drives human sost expression in osteoblast-like cell lines in vitro and in the skeletal anlage of the E14.5 mouse embryo, and discovered a novel function for sclerostin during limb development. Our approach represents a framework for characterizing distant regulatory elements associated with abnormal human phenotypes.

  19. Ion beam analysis of the bone tissue of Alzheimer's disease patients

    NASA Astrophysics Data System (ADS)

    Robertson, J. D.; Samudralwar, D. L.; Markesbery, W. R.

    1992-02-01

    It has been hypothesized that perturbations in element metabolism play a role in the etiology and/or pathogenesis of Alzheimer's disease (AD). No conclusion regarding this hypothesis has been reached, however, as results for central nervous system tissues from different research groups are contradictory. We are currently utilizing external-beam thick-target FIXE and PIGE analyses to investigate the elemental concentrations in the bone tissue of AD patients. Because bone acts as a "repository" for many trace elements, these measurements should provide information on the long-term trace-element status of AD patients. With the simultaneous PIXE/PIGE measurements, we are able to instrumentally determine the concentrations of oxygen, phosphorus, calcium, and 12-15 minor and trace elements in a single 30 min irradiation. Initial results obtained from the IBA measurements of both cortical and trabecular bone autopsy samples from four AD patients and twelve age-matched controls indicate a possible imbalance in Zn, Br and Rb.

  20. Coping with time scales in disease systems analysis: application to bone remodeling.

    PubMed

    Schmidt, Stephan; Post, Teun M; Peletier, Lambertus A; Boroujerdi, Massoud A; Danhof, Meindert

    2011-12-01

    In this study we demonstrate the added value of mathematical model reduction for characterizing complex dynamic systems using bone remodeling as an example. We show that for the given parameter values, the mechanistic RANK-RANKL-OPG pathway model proposed by Lemaire et al. (J Theor Biol 229:293-309, 2004) can be reduced to a simpler model, which can describe the dynamics of the full Lemaire model to very good approximation. The response of both models to changes in the underlying physiology and therapeutic interventions was evaluated in four physiologically meaningful scenarios: (i) estrogen deficiency/estrogen replacement therapy, (ii) Vitamin D deficiency, (iii) ageing, and (iv) chronic glucocorticoid treatment and its cessation. It was found that on the time scale of disease progression and therapeutic intervention, the models showed negligible differences in their dynamic properties and were both suitable for characterizing the impact of estrogen deficiency and estrogen replacement therapy, Vitamin D deficiency, ageing, and chronic glucocorticoid treatment and its cessation on bone forming (osteoblasts) and bone resorbing (osteoclasts) cells. It was also demonstrated how the simpler model could help in elucidating qualitative properties of the observed dynamics, such as the absence of overshoot and rebound, and the different dynamics of onset and washout.

  1. Osteoporosis: Modern Paradigms for Last Century’s Bones

    PubMed Central

    Kruger, Marlena C.; Wolber, Frances M.

    2016-01-01

    The skeleton is a metabolically active organ undergoing continuously remodelling. With ageing and menopause the balance shifts to increased resorption, leading to a reduction in bone mineral density and disruption of bone microarchitecture. Bone mass accretion and bone metabolism are influenced by systemic hormones as well as genetic and lifestyle factors. The classic paradigm has described osteoporosis as being a “brittle bone” disease that occurs in post-menopausal, thin, Caucasian women with low calcium intakes and/or vitamin D insufficiency. However, a study of black women in Africa demonstrated that higher proportions of body fat did not protect bone health. Isoflavone interventions in Asian postmenopausal women have produced inconsistent bone health benefits, due in part to population heterogeneity in enteric bacterial metabolism of daidzein. A comparison of women and men in several Asian countries identified significant differences between countries in the rate of bone health decline, and a high incidence rate of osteoporosis in both sexes. These studies have revealed significant differences in genetic phenotypes, debunking long-held beliefs and leading to new paradigms in study design. Current studies are now being specifically designed to assess genotype differences between Caucasian, Asian, African, and other phenotypes, and exploring alternative methodology to measure bone architecture. PMID:27322315

  2. Increased serum IgE concentrations during infection and graft versus host disease after bone marrow transplantation.

    PubMed Central

    Walker, S A; Rogers, T R; Perry, D; Hobbs, J R; Riches, P G

    1984-01-01

    Serum IgE concentrations estimated in 25 bone marrow transplant recipients during episodes of infection or graft versus host disease, or both, were raised not only in some patients with acute graft versus host disease but also in many patients with infection. Raised values were not seen in chronic graft versus host disease. The routine estimation of serum IgE in bone marrow transplant recipients had minimal value because of the lack of specificity of the IgE response. PMID:6368605

  3. A "bone marrow score" for predicting hematological disease in immunocompetent patients with fevers of unknown origin.

    PubMed

    Wang, Hao-Yuan; Yang, Ching-Fen; Chiou, Tzeon-Jye; Yang, Sheng-Hsiang; Gau, Jyh-Pyng; Yu, Yuan-Bin; Liu, Chun-Yu; Liu, Jin-Hwang; Chen, Po-Min; Hsu, Hui-Chi; Fung, Chang-Phone; Tzeng, Cheng-Hwai; Hsiao, Liang-Tsai

    2014-12-01

    Delayed diagnosis of hematological malignancies in immunocompetent patients with fever of unknown origin (FUO) remains an exhausting challenge for non-hematologist physicians. This retrospective cohort study aimed to establish a scoring system, "bone marrow (BM) score", to identify FUO patients who require early bone marrow biopsy (BMB) to diagnose hematological disease. Two cohorts, comprising 85 (training) and 20 (validation) eligible immunocompetent patients, with FUOs diagnosed between January 1, 2006 and July 31, 2013, underwent BMBs and were enrolled in the study. Demographic, laboratory, imaging, diagnostic, and outcome data were collected and retrospectively analyzed. Factors associated with hematological etiologies diagnosed using BMBs in the training cohort were identified and scored according to the relative hazards. These were further validated using the validation cohort. For the training cohort, 29 of 85 (34.1%) patients had hematological etiologies diagnosed using BMB. Seven factors significantly predicted the diagnostic yield of hematological diseases in the BM and were scored, with the 6 points for leucoerythroblastic changes in peripheral blood smears, 5.5 for elevated ferritin level (>1000 ng/mL), 4 for splenomegaly, 2 for thrombocytopenia, 1.5 for each of elevated lactate dehydrogenase levels and anemia, and 1 for neutropenia. When the cut-off value of the scoring system was set to 6, its sensitivity and specificity to diagnose hematological diseases in the BM of immunocompetent FUO patients were 93% and 58%, respectively. For the validation cohort, 7 of 20 (35%) patients had hematological disease, and all had BM scores higher than the cut-off, with the sensitivity and specificity at 100% and 77%, respectively. As immunocompetent FUO patients with hematological disease have poor prognoses, the "BM score" is valuable for non-hematologist physicians to identify immunocompetent FUO patients requiring early BMB.

  4. A phase IIa, nonrandomized study of radium-223 dichloride in advanced breast cancer patients with bone-dominant disease.

    PubMed

    Coleman, Robert; Aksnes, Anne-Kirsti; Naume, Bjørn; Garcia, Camilo; Jerusalem, Guy; Piccart, Martine; Vobecky, Nancy; Thuresson, Marcus; Flamen, Patrick

    2014-06-01

    Radium-223 dichloride (radium-223) mimics calcium and emits high-energy, short-range alpha-particles resulting in an antitumor effect on bone metastases. This open-label, phase IIa nonrandomized study investigated safety and short-term efficacy of radium-223 in breast cancer patients with bone-dominant disease. Twenty-three advanced breast cancer patients with progressive bone-dominant disease, and no longer candidates for further endocrine therapy, were to receive radium-223 (50 kBq/kg IV) every 4 weeks for 4 cycles. The coprimary end points were change in urinary N-telopeptide of type 1 (uNTX-1) and serum bone alkaline phosphatase (bALP) after 16 weeks of treatment. Exploratory end points included sequential (18)F-fluorodeoxyglucose positron emission tomography and computed tomography (FDG PET/CT) to assess metabolic changes in osteoblastic bone metastases. Safety data were collected for all patients. Radium-223 significantly reduced uNTX-1 and bALP from baseline to end of treatment. Median uNTX-1 change was -10.1 nmol bone collagen equivalents/mmol creatinine (-32.8 %; P = 0.0124); median bALP change was -16.7 ng/mL (-42.0 %; P = 0.0045). Twenty of twenty-three patients had FDG PET/CT identifying 155 hypermetabolic osteoblastic bone lesions at baseline: 50 lesions showed metabolic decrease (≥25 % reduction of maximum standardized uptake value from baseline) after 2 radium-223 injections [32.3 % metabolic response rate (mRR) at week 9], persisting after the treatment period (41.5 % mRR at week 17). Radium-223 was safe and well tolerated. Radium-223 targets areas of increased bone metabolism and shows biological activity in advanced breast cancer patients with bone-dominant disease.

  5. The Impact of Conventional and Biological Disease Modifying Antirheumatic Drugs on Bone Biology. Rheumatoid Arthritis as a Case Study.

    PubMed

    Barreira, Sofia Carvalho; Fonseca, João Eurico

    2016-08-01

    The bone and the immune system have a very tight interaction. Systemic immune-mediated inflammatory diseases, such as rheumatoid arthritis (RA), induce bone loss, leading to a twofold increase in osteoporosis and an increase of fragility fracture risk of 1.35-2.13 times. This review focuses on the effects of conventional and biological disease modifying antirheumatic drugs (DMARDs) on bone biology, in the context of systemic inflammation, with a focus on RA. Published evidence supports a decrease in osteoclastic activity induced by DMARDs, which leads to positive effects on bone mineral density (BMD). It is unknown if this effect could be translated into fracture risk reduction. The combination with antiosteoclastic drugs can have an additional benefit.

  6. Bone Analyzer

    NASA Technical Reports Server (NTRS)

    1985-01-01

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

  7. Controlled crack growth specimen for brittle systems

    NASA Technical Reports Server (NTRS)

    Calomino, Anthony M.; Brewer, David N.

    1992-01-01

    A pure Mode 1 fracture specimen and test procedure has been developed which provides extended, stable, through-thickness crack growth in ceramics and other brittle, nonmetallic materials. Fixed displacement loading, applied at the crack mouth, promotes stable crack extension by reducing the stored elastic strain energy. Extremely fine control of applied displacements is achieved by utilizing the Poisson's expansion of a compressively loaded cylindrical pin. Stable cracks were successfully grown in soda-lime glass and monolithic Al2O3 for lengths in excess of 2O mm without uncontrollable catastrophic failure.

  8. Controlled crack growth specimen for brittle systems

    NASA Technical Reports Server (NTRS)

    Calomino, Anthony M.; Brewer, David N.

    1990-01-01

    A pure Mode 1 fracture specimen and test procedure has been developed which provides extended, stable, through-thickness crack growth in ceramics and other brittle, nonmetallic materials. Fixed displacement loading, applied at the crack mouth, promotes stable crack extension by reducing the stored elastic strain energy. Extremely fine control of applied displacements is achieved by utilizing the Poisson's expansion of a compressively loaded cylindrical pin. Stable cracks were successfully grown in soda-lime glass and monolithic Al2O3 for lengths in excess of 20 mm without uncontrollable catastrophic failure.

  9. Factors that affect postnatal bone growth retardation in the twitcher murine model of Krabbe disease.

    PubMed

    Contreras, Miguel Agustin; Ries, William Louis; Shanmugarajan, Srinivasan; Arboleda, Gonzalo; Singh, Inderjit; Singh, Avtar Kaur

    2010-01-01

    Krabbe disease is an inherited lysosomal disorder in which galactosylsphingosine (psychosine) accumulates mainly in the central nervous system. To gain insight into the possible mechanism(s) that may be participating in the inhibition of the postnatal somatic growth described in the animal model of this disease (twitcher mouse, twi), we studied their femora. This study reports that twi femora are smaller than of those of wild type (wt), and present with abnormality of marrow cellularity, bone deposition (osteoblastic function), and osteoclastic activity. Furthermore, lipidomic analysis indicates altered sphingolipid homeostasis, but without significant changes in the levels of sphingolipid-derived intermediates of cell death (ceramide) or the levels of the osteoclast-osteoblast coupling factor (sphingosine-1-phosphate). However, there was significant accumulation of psychosine in the femora of adult twi animals as compared to wt, without induction of tumor necrosis factor-alpha or interleukin-6. Analysis of insulin-like growth factor-1 (IGF-1) plasma levels, a liver secreted hormone known to play a role in bone growth, indicated a drastic reduction in twi animals when compared to wt. To identify the cause of the decrease, we examined the IGF-1 mRNA expression and protein levels in the liver. The results indicated a significant reduction of IGF-1 mRNA as well as protein levels in the liver from twi as compared to wt littermates. Our data suggest that a combination of endogenous (psychosine) and endocrine (IGF-1) factors play a role in the inhibition of postnatal bone growth in twi mice; and further suggest that derangements of liver function may be contributing, at least in part, to this alteration.

  10. [Implications of the new etiophatogenic approach in the classification of constitutional and genetic bone diseases].

    PubMed

    Morales Piga, Antonio; Alonso Ferreira, Verónica; Villaverde-Hueso, Ana

    2011-01-01

    Recent years have seen an unprecedented increase in the knowledge and understanding of biochemical disturbances involved on constitutional bone disorders. Recognition of the genetic background as the common cause of these diseases prompted the substitution of the term «constitutional» by «genetic», in referring to them. Understanding physiopathological bases by finding out the altered metabolic pathways as well as their regulatory and control systems, favours an earlier and more accurate diagnosis based on interdisciplinary collaboration. Although clinical and radiological assessment remains crucial in the study of these disorders, ever more often the diagnosis is achieved by molecular and genetic analysis. Elucidation of the damaged underlying molecular mechanisms offers targets potentially useful for therapeutic research in these complex and often disabling diseases.

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

    PubMed Central

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

    2015-01-01

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

  12. Bone mass and vitamin D levels in Parkinson’s disease: is there any difference between genders?

    PubMed Central

    Ozturk, Erhan Arif; Gundogdu, Ibrahim; Tonuk, Burak; Kocer, Bilge Gonenli; Tombak, Yasemin; Comoglu, Selcuk; Cakci, Aytul

    2016-01-01

    [Purpose] The aim of this study was to determine the bone mineral density, vitamin D level, and frequencies of osteopenia and osteoporosis in patients with Parkinson’s disease and to compare male and female patients with the controls separately. [Subjects and Methods] One hundred fifteen Parkinson’s disease patients (47 males, 68 females; age range: 55–85 years) and 117 age- and gender-matched controls (47 males, 70 females) were enrolled in the study. Bone mineral density measured by dual-energy X-ray absorptiometry and serum D vitamin levels of each participant were recorded. [Results] The mean lumbar spine, femur neck, and total femur bone mineral density levels, T-scores, and vitamin D levels were found to be significantly lower in Parkinson’s disease patients in both genders. Furthermore, osteoporosis rates were found be significantly higher only in female Parkinson’s disease patients compared with female controls. [Conclusion] Data from the present study revealed that while osteoporosis was significantly higher only in female Parkinson’s disease patients, all Parkinson’s disease patients had lower bone mineral density scores and vitamin D levels compared with the controls regardless of gender, suggesting that clinicians should pay attention to the osteoporosis risk in Parkinson’s disease and that adequate preventive measures should be taken in order to limit the future risk due to osteoporotic fractures. PMID:27630398

  13. Brittle and semi-brittle behaviours of a carbonate rock: influence of water and temperature

    NASA Astrophysics Data System (ADS)

    Nicolas, A.; Fortin, J.; Regnet, J. B.; Dimanov, A.; Guéguen, Y.

    2016-07-01

    Inelastic deformation can either occur with dilatancy or compaction, implying differences in porosity changes, failure and petrophysical properties. In this study, the roles of water as a pore fluid, and of temperature, on the deformation and failure of a micritic limestone (white Tavel limestone, porosity 14.7 per cent) were investigated under triaxial stresses. For each sample, a hydrostatic load was applied up to the desired confining pressure (from 0 up to 85 MPa) at either room temperature or at 70 °C. Two pore fluid conditions were investigated at room temperature: dry and water saturated. The samples were deformed up to failure at a constant strain rate of ˜10-5 s-1. The experiments were coupled with ultrasonic wave velocity surveys to monitor crack densities. The linear trend between the axial crack density and the relative volumetric strain beyond the onset of dilatancy suggests that cracks propagate at constant aspect ratio. The decrease of ultrasonic wave velocities beyond the onset of inelastic compaction in the semi-brittle regime indicates the ongoing interplay of shear-enhanced compaction and crack development. Water has a weakening effect on the onset of dilatancy in the brittle regime, but no measurable influence on the peak strength. Temperature lowers the confining pressure at which the brittle-semi-brittle transition is observed but does not change the stress states at the onset of inelastic compaction and at the post-yield onset of dilatancy.

  14. Bone metabolism status and associated risk factors in elderly patients with chronic obstructive pulmonary disease (COPD).

    PubMed

    Xiaomei, Wang; Hang, Xiao; Lingling, Liu; Xuejun, Li

    2014-09-01

    The prevalence of osteoporosis in older patients with chronic obstructive pulmonary disease (COPD) is higher than in the age-matched elderly patients, but the exact cause in relation to COPD is not clear. We hypothesized that the underlying causes for this difference are related to bone metabolism with the possible risk factors that include the duration of COPD, GOLD grade, cor pulmonale, the frequencies of acute exacerbations within the past year, smoking and inhaled corticosteroid therapy. We conducted a matched-pair study of 100 patients aged older than 65 years at the Southwest Hospital from May to November 2012. The enrolled patients with COPD were matched to controls for age and gender. Clinical characteristics of cohorts were recorded. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry and osteoporosis was diagnosed according to the definition of WHO. All cohorts accepted bone metabolism marker measurement, including Procollagen type 1 aminoterminal propeptide (P1NP), β-C-telopeptides of type I collagen (βCTX), and N-terminal midmolecule fragment osteocalcin (N-MID OC). Statistical analysis was calculated using the student's t test, ANOVA and multiple regression analysis at a significance level set at a p < 0.05. Circulating biochemical markers of bone formation (P1NP), resorption (βCTX) and turnover (N-MID OC) were significantly lower in the COPD group than control group, while mean 25-OH Vitamin D was similar in two groups. The P1NP, βCTX, and N-MID OC were still lower in men with COPD, but only P1NP was lower in women with COPD compared to that of controls. Multiple regression analysis in COPD group suggests that age, the frequency of acute exacerbation, and BMD are independent risk factors for P1NP. The frequency of acute exacerbation within the past one year and 25-OH D level are independent risk factors for βCTX; the frequency of acute exacerbation is the only independent risk factor for N-MID OC. These were significant

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

    PubMed Central

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

    2016-01-01

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

  16. Brittle superconducting magnets: an equivilent strain model

    SciTech Connect

    Barzi, E.; Danuso, M.

    2010-08-01

    To exceed fields of 10 T in accelerator magnets, brittle superconductors like A15 Nb{sub 3}Sn and Nb{sub 3}Al or ceramic High Temperature Superconductors have to be used. For such brittle superconductors it is not their maximum tensile yield stress that limits their structural resistance as much as strain values that provoke deformations in their delicate lattice, which in turn affect their superconducting properties. Work on the sensitivity of Nb{sub 3}Sn cables to strain has been conducted in a number of stress states, including uniaxial and multi-axial, producing usually different results. This has made the need of a constituent design criterion imperative for magnet builders. In conventional structural problems an equivalent stress model is typically used to verify mechanical soundness. In the superconducting community a simple scalar equivalent strain to be used in place of an equivalent stress would be an extremely useful tool. As is well known in fundamental mechanics, there is not one single way to reduce a multiaxial strain state as represented by a 2nd order tensor to a scalar. The conceptual experiment proposed here will help determine the best scalar representation to use in the identification of an equivalent strain model.

  17. Phase field approximation of dynamic brittle fracture

    NASA Astrophysics Data System (ADS)

    Schlüter, Alexander; Willenbücher, Adrian; Kuhn, Charlotte; Müller, Ralf

    2014-11-01

    Numerical methods that are able to predict the failure of technical structures due to fracture are important in many engineering applications. One of these approaches, the so-called phase field method, represents cracks by means of an additional continuous field variable. This strategy avoids some of the main drawbacks of a sharp interface description of cracks. For example, it is not necessary to track or model crack faces explicitly, which allows a simple algorithmic treatment. The phase field model for brittle fracture presented in Kuhn and Müller (Eng Fract Mech 77(18):3625-3634, 2010) assumes quasi-static loading conditions. However dynamic effects have a great impact on the crack growth in many practical applications. Therefore this investigation presents an extension of the quasi-static phase field model for fracture from Kuhn and Müller (Eng Fract Mech 77(18):3625-3634, 2010) to the dynamic case. First of all Hamilton's principle is applied to derive a coupled set of Euler-Lagrange equations that govern the mechanical behaviour of the body as well as the crack growth. Subsequently the model is implemented in a finite element scheme which allows to solve several test problems numerically. The numerical examples illustrate the capabilities of the developed approach to dynamic fracture in brittle materials.

  18. In silico investigations of the anti-catabolic effects of pamidronate and denosumab on multiple myeloma-induced bone disease.

    PubMed

    Wang, Yan; Lin, Bo

    2012-01-01

    It is unclear whether the new anti-catabolic agent denosumab represents a viable alternative to the widely used anti-catabolic agent pamidronate in the treatment of Multiple Myeloma (MM)-induced bone disease. This lack of clarity primarily stems from the lack of sufficient clinical investigations, which are costly and time consuming. However, in silico investigations require less time and expense, suggesting that they may be a useful complement to traditional clinical investigations. In this paper, we aim to (i) develop integrated computational models that are suitable for investigating the effects of pamidronate and denosumab on MM-induced bone disease and (ii) evaluate the responses to pamidronate and denosumab treatments using these integrated models. To achieve these goals, pharmacokinetic models of pamidronate and denosumab are first developed and then calibrated and validated using different clinical datasets. Next, the integrated computational models are developed by incorporating the simulated transient concentrations of pamidronate and denosumab and simulations of their actions on the MM-bone compartment into the previously proposed MM-bone model. These integrated models are further calibrated and validated by different clinical datasets so that they are suitable to be applied to investigate the responses to the pamidronate and denosumab treatments. Finally, these responses are evaluated by quantifying the bone volume, bone turnover, and MM-cell density. This evaluation identifies four denosumab regimes that potentially produce an overall improved bone-related response compared with the recommended pamidronate regime. This in silico investigation supports the idea that denosumab represents an appropriate alternative to pamidronate in the treatment of MM-induced bone disease.

  19. A Geometrically Nonlinear Phase Field Theory of Brittle Fracture

    DTIC Science & Technology

    2014-10-01

    A Geometrically Nonlinear Phase Field Theory of Brittle Fracture by JD Clayton and J Knap ARL-RP-0511 October 2014...21005-5069 ARL-RP-0511 October 2014 A Geometrically Nonlinear Phase Field Theory of Brittle Fracture JD Clayton and J Knap Weapons and...Nonlinear Phase Field Theory of Brittle Fracture 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) JD Clayton

  20. Bilateral Inflammatory Optic Neuropathy Related to Graft versus Host Disease Following Allogeneic Bone Marrow Transplantation for Hodgkin Disease

    PubMed Central

    Moesen, I.; Kidd, D. P.

    2014-01-01

    Abstract Graft versus host disease (GvHD) is a common and often troublesome complication of allogeneic bone marrow transplantation. Neurological complications usually involve the peripheral nervous system and muscle, but the central nervous system may be affected. When an optic neuropathy develops, it is often difficult to determine the cause quickly; infective complications and drug toxicity may have arisen, but an inflammatory disorder due to GvHD should also be considered, particularly since treatment with steroids and immune suppression may improve the outcome significantly. This brief case report shows how this may be the case and reviews our current understanding of the pathophysiology and treatment of the disorder within the nervous system. PMID:27928304

  1. NONDESTRUCTIVE ANALYSIS OF THE BRITTLE FRACTURE BEHAVIOR OF CERAMIC MATERIALS

    DTIC Science & Technology

    CERAMIC MATERIALS , *NONDESTRUCTIVE TESTING, BRITTLENESS, DIELECTRIC PROPERTIES, DIFFUSION, ELASTIC PROPERTIES, FRACTURE (MECHANICS), IMPURITIES, MECHANICAL PROPERTIES, RESONANCE, STRESSES, THERMAL DIFFUSION, THERMAL STRESSES

  2. Novel Lesions of Bones and Joints Associated with Chikungunya Virus Infection in Two Mouse Models of Disease: New Insights into Disease Pathogenesis

    PubMed Central

    Goupil, Brad A.; McNulty, Margaret A.; Martin, Matthew J.; McCracken, Michael K.; Christofferson, Rebecca C.; Mores, Christopher N.

    2016-01-01

    Chikungunya virus is an arbovirus spread predominantly by Aedes aegypti and Ae. albopictus mosquitoes, and causes debilitating arthralgia and arthritis. While these are common manifestations during acute infection and it has been suggested they can recur in patients chronically, gaps in knowledge regarding the pathogenesis still exist. Two established mouse models were utilized (adult IRF 3/7 -/- -/- and wild-type C57BL/6J mice) to evaluate disease manifestations in bones and joints at various timepoints. Novel lesions in C57BL/6J mice consisted of periostitis (91%) and foci of cartilage of necrosis (50% of mice at 21 DPI). Additionally, at 21 DPI, 50% and 75% of mice exhibited periosteal bone proliferation affecting the metatarsal bones, apparent via histology and μCT, respectively. μCT analysis did not reveal any alterations in trabecular bone volume measurements in C57BL/6J mice. Novel lesions demonstrated in IRF 3/7 -/- -/- mice at 5 DPI included focal regions of cartilage necrosis (20%), periosteal necrosis (66%), and multifocal ischemic bone marrow necrosis (100%). Contralateral feet in 100% of mice of both strains had similar, though milder lesions. Additionally, comparison of control IRF 3/7 -/- -/- and wild-type C57BL/6J mice demonstrated differences in cortical bone. These experiments demonstrate novel manifestations of disease similar to those occurring in humans, adding insight into disease pathogenesis, and representing new potential targets for therapeutic interventions. Additionally, results demonstrate the utility of μCT in studies of bone and joint pathology and illustrate differences in bone dynamics between mouse strains. PMID:27182740

  3. Low serum and bone vitamin K status in patients with longstanding Crohn's disease: another pathogenetic factor of osteoporosis in Crohn's disease?

    PubMed Central

    Schoon, E; Muller, M; Vermeer, C; Schurgers, L; Brummer, R; Stockbrugger, R

    2001-01-01

    BACKGROUND—A high prevalence of osteoporosis is reported in Crohn's disease. The pathogenesis is not completely understood but is probably multifactorial. Longstanding Crohn's disease is associated with a deficiency of fat soluble vitamins, among them vitamin K. Vitamin K is a cofactor in the carboxylation of osteocalcin, a protein essential for calcium binding to bone. A high level of circulating uncarboxylated osteocalcin is a sensitive marker of vitamin K deficiency.
AIMS—To determine serum and bone vitamin K status in patients with Crohn's disease and to elucidate its relationship with bone mineral density.
METHODS—Bone mineral density was measured in 32 patients with longstanding Crohn's disease and small bowel involvement, currently in remission, and receiving less than 5 mg of prednisolone daily. Serum levels of vitamins D and K, triglycerides, and total immunoreactive osteocalcin, as well as uncarboxylated osteocalcin ("free" osteocalcin) were determined. The hydroxyapatite binding capacity of osteocalcin was calculated. Data were compared with an age and sex matched control population.
RESULTS—Serum vitamin K levels of CD patients were significantly decreased compared with normal controls (p<0.01). "Free" osteocalcin was higher and hydroxyapatite binding capacity of circulating osteocalcin was lower than in matched controls (p<0.05 and p<0.001, respectively), indicating a low bone vitamin K status in Crohn's disease. In patients, an inverse correlation was found between "free" osteocalcin and lumbar spine bone mineral density (r=−0.375, p<0.05) and between "free" osteocalcin and the z score of the lumbar spine (r=−0.381, p<0.05). Multiple linear regression analysis showed that "free" osteocalcin was an independent risk factor for low bone mineral density of the lumbar spine whereas serum vitamin D was not.
CONCLUSIONS—The finding that a poor vitamin K status is associated with low bone mineral density in longstanding Crohn

  4. Approach to diagnosing celiac disease in patients with low bone mineral density or fragility fractures

    PubMed Central

    Rios, Lorena P.; Khan, Aliya; Sultan, Muhammad; McAssey, Karen; Fouda, Mona A.; Armstrong, David

    2013-01-01

    Abstract Objective To provide clinicians with an update on the diagnosis of celiac disease (CD) and to make recommendations on the indications to screen for CD in patients presenting with low bone mineral density (BMD) or fragility fractures. Quality of evidence A multidisciplinary task force developed clinically relevant questions related to the diagnosis of CD as the basis for a literature search of the MEDLINE, EMBASE, and CENTRAL databases (January 2000 to January 2009) using the key words celiac disease, osteoporosis, osteopenia, low bone mass, and fracture. The existing literature consists of level I and II studies. Main message The estimated prevalence of asymptomatic CD is 2% to 3% in individuals with low BMD. Routine screening for CD is not justified in patients with low BMD. However, targeted screening for CD is recommended for patients who have T-scores of −1.0 or less at the spine or hip, or a history of fragility fractures in association with any CD-related symptoms or conditions; family history of CD; or low urinary calcium levels, vitamin D insufficiency, and raised parathyroid hormone levels despite adequate intake of calcium and vitamin D. Celiac disease testing should be performed while the subject is consuming a gluten-containing diet; initial screening should be performed with human recombinant immunoglobulin (Ig) A tissue transglutaminase or other IgA tissue transglutaminase assays, in association with IgA endomysial antibody immunofluorescence. Duodenal biopsy is necessary to confirm the diagnosis of CD. Human leukocyte antigen typing might assist in confirming or ruling out the diagnosis of CD in cases where serology and histology are discordant. Definitive diagnosis is based on clinical, serologic, and histologic features, combined with a positive response to a gluten-free diet. Conclusion Current evidence does not support routine screening for CD in all patients with low BMD. A targeted case-finding approach is appropriate for patients

  5. A 3-D analysis of the protympanum in human temporal bones with chronic ear disease.

    PubMed

    Pauna, Henrique F; Monsanto, Rafael C; Schachern, Patricia; Paparella, Michael M; Cureoglu, Sebahattin

    2017-03-01

    Eustachian tube dysfunction is believed to be an important factor to cholesteatoma development and recurrence of disease after surgical treatment. Although many studies have described prognostic factors, evaluation methods, or surgical techniques for Eustachian tube dysfunction, they relied on the soft tissues of its structure; little is known about its bony structure-the protympanum-which connects the Eustachian tube to the tympanic cavity, and can also be affected by several inflammatory conditions, both from the middle ear or from the nasopharynx. We studied temporal bones from patients with cholesteatoma, chronic otitis media (with and without retraction pockets), purulent otitis media, and non-diseased ears, looking for differences between the volume of the protympanum, the diameter of the Eustachian tube isthmus, and the distance between the anterior tympanic annulus and the promontory. Light microscopy and 3-D reconstruction software were used for the measurements. We observed a decrease of volume in the lumen of the four middle ear diseased ears compared to the control group. We observed a significant decrease in the volume of the protympanic space in the cholesteatoma group compared to the chronic otitis media group. We also observed a decrease in the bony space (protympanum space) in cholesteatoma, chronic otitis media with retraction pockets, and purulent otitis media compared to the control group. We found a correlation in middle ear diseases and a decrease in the middle ear space. Our findings may suggest that a smaller bony volume in the protympanic area may trigger middle ear dysventilation problems.

  6. Stem cell bone marrow transplantation in patients with metabolic storage diseases.

    PubMed

    Krivit, William

    2002-01-01

    In 1984, an initial report was published on the use of BMT for inborn errors of metabolism. Our first BMT patient had a diagnosis of Maroteaux-Lamy syndrome. She had end-stage cardiopulmonary disease at the time of the transplant and was considered likely to die within months. (69) She is still alive 2 decades later, albeit with limited pulmonary function. In 1992, experimental data demonstrated the prevention of CNS deterioration in fucosidase-deficient dogs after BMT.70 These findings have been noted in many other similar studies. (46) Ample data indicate that BMT can reconstitute the CNS in several of these diseases. Progress is continuing in reducing the morbidity and mortality. In the near future, additional advances may allow for no loss of life and no illness during the bone marrow transplantation process. There is hope that by using neonatal screening techniques, infants at risk can have metabolic storage diseases diagnosed before the diseases progress so that effective treatment can be provided. The combination of all of these advances should result in a logarithmic improvement within the next 2 decades. The plan will be to avoid any mortality or morbidity and to always provide complete engraftment that is permanent and enters all tissues completely.

  7. Aging accentuates and bone marrow transplantation ameliorates metabolic defects in Fabry disease mice

    PubMed Central

    Ohshima, Toshio; Schiffmann, Raphael; Murray, Gary J.; Kopp, Jeffrey; Quirk, Jane M.; Stahl, Stefanie; Chan, Chi-Chao; Zerfas, Patricia; Tao-Cheng, Jung-Hwa; Ward, J. M.; Brady, Roscoe O.; Kulkarni, Ashok B.

    1999-01-01

    Fabry disease is an X-linked metabolic disorder caused by a deficiency of α-galactosidase A (α-Gal A). The enzyme defect leads to the systemic accumulation of glycosphingolipids with α-galactosyl moieties consisting predominantly of globotriaosylceramide (Gb3). In patients with this disorder, glycolipid deposition in endothelial cells leads to renal failure and cardiac and cerebrovascular disease. Recently, we generated α-Gal A gene knockout mouse lines and described the phenotype of 10-week-old mice. In the present study, we characterize the progression of the disease with aging and explore the effects of bone marrow transplantation (BMT) on the phenotype. Histopathological analysis of α-Gal A −/0 mice revealed subclinical lesions in the Kupffer cells in the liver and macrophages in the skin with no gross lesions in the endothelial cells. Gb3 accumulation and pathological lesions in the affected organs increased with age. Treatment with BMT from the wild-type mice resulted in the clearance of accumulated Gb3 in the liver, spleen, and heart with concomitant elevation of α-Gal A activity. These findings suggest that BMT may have a potential role in the management of patients with Fabry disease. PMID:10339603

  8. Pulmonary, gonadal, and central nervous system status after bone marrow transplantation for sickle cell disease.

    PubMed

    Walters, Mark C; Hardy, Karen; Edwards, Sandie; Adamkiewicz, Thomas; Barkovich, James; Bernaudin, Francoise; Buchanan, George R; Bunin, Nancy; Dickerhoff, Roswitha; Giller, Roger; Haut, Paul R; Horan, John; Hsu, Lewis L; Kamani, Naynesh; Levine, John E; Margolis, David; Ohene-Frempong, Kwaku; Patience, Melinda; Redding-Lallinger, Rupa; Roberts, Irene A G; Rogers, Zora R; Sanders, Jean E; Scott, J Paul; Sullivan, Keith M

    2010-02-01

    We conducted a prospective, multicenter investigation of human-leukocyte antigen (HLA) identical sibling bone marrow transplantation (BMT) in children with severe sickle cell disease (SCD) between 1991 and 2000. To determine if children were protected from complications of SCD after successful BMT, we extended our initial study of BMT for SCD to conduct assessments of the central nervous system (CNS) and of pulmonary function 2 or more years after transplantation. In addition, the impact on gonadal function was studied. After BMT, patients with stroke who had stable engraftment of donor cells experienced no subsequent stroke events after BMT, and brain magnetic resonance imaging (MRI) exams demonstrated stable or improved appearance. However, 2 patients with graft rejection had a second stroke after BMT. After transplantation, most patients also had unchanged or improved pulmonary function. Among the 11 patients who had restrictive lung changes at baseline, 5 were improved and 6 had persistent restrictive disease after BMT. Of the 2 patients who had obstructive changes at baseline, 1 improved and 1 had worsened obstructive disease after BMT. There was, however, significant gonadal toxicity after BMT, particularly among female recipients. In summary, individuals who had stable donor engraftment did not experience sickle-related complications after BMT, and were protected from progressive CNS and pulmonary disease.

  9. Platelet dysfunction and a high bone mass phenotype in a murine model of platelet-type von Willebrand disease.

    PubMed

    Suva, Larry J; Hartman, Eric; Dilley, Joshua D; Russell, Susan; Akel, Nisreen S; Skinner, Robert A; Hogue, William R; Budde, Ulrich; Varughese, Kottayil I; Kanaji, Taisuke; Ware, Jerry

    2008-02-01

    The platelet glycoprotein Ib-IX receptor binds surface-bound von Willebrand factor and supports platelet adhesion to damaged vascular surfaces. A limited number of mutations within the glycoprotein Ib-IX complex have been described that permit a structurally altered receptor to interact with soluble von Willebrand factor, and this is the molecular basis of platelet-type von Willebrand disease. We have developed and characterized a mouse model of platelet-type von Willebrand disease (G233V) and have confirmed a platelet phenotype mimicking the human disorder. The mice have a dramatic increase in splenic megakaryocytes and splenomegaly. Recent studies have demonstrated that hematopoetic cells can influence the differentiation of osteogenic cells. Thus, we examined the skeletal phenotype of mice expressing the G233V variant complex. At 6 months of age, G233V mice exhibit a high bone mass phenotype with an approximate doubling of trabecular bone volume in both the tibia and femur. Serum measures of bone resorption were significantly decreased in G233V animals. With decreased bone resorption, cortical thickness was increased, medullary area decreased, and consequently, the mechanical strength of the femur was significantly increased. Using ex vivo bone marrow cultures, osteoclast-specific staining in the G233V mutant marrow was diminished, whereas osteoblastogenesis was unaffected. These studies provide new insights into the relationship between the regulation of megakaryocytopoiesis and bone mass.

  10. Vitamin D Status and Bone Mineral Density in Obese Children with Nonalcoholic Fatty Liver Disease

    PubMed Central

    2015-01-01

    Whether nonalcoholic fatty liver disease (NAFLD) is related to vitamin D and bone health in obese children is unknown. The aim of this study was to evaluate vitamin D status and bone mineral density (BMD) in obese children according to their condition within the NAFLD spectrum. Anthropometric data, laboratory tests, and abdominal ultrasonography were obtained from 94 obese children. The subjects were divided into three groups according to NAFLD spectrum: normal liver, simple steatosis, and nonalcoholic steatohepatitis (NASH). Although there were no differences in vitamin D levels between the three groups, these groups showed significant differences in highly sensitive C-reactive protein (P=0.044), homeostasis model assessment of insulin resistance (HOMA-IR) (P=0.02), hepatic fibrosis scores (P<0.05), and trunk fat percentage (P=0.025). Although there were significant differences in BMDs, the age-matched BMD z-scores were not significantly different between the three groups. Serum vitamin D levels were negatively correlated with age (r=-0.368, P=0.023), serum uric acid levels (r=-0.371, P=0.022), fibrosis 4 (FIB4) (r=-0.406, P=0.011), and HOMA-IR (r=-0.530, P=0.001) in obese children with NASH. Multiple regression analysis for vitamin D in the NASH group revealed age and HOMA-IR as significant factors. In conclusion, inflammatory markers, hepatic fibrosis scores, trunk fat, and insulin resistance may reflect the spectrum of NAFLD in obese children, whereas vitamin D levels and BMD may not. In patients with NASH, however, low serum vitamin D is associated with hepatic fibrosis and insulin resistance, but not with bone health status. PMID:26713058

  11. Evaluation of Bone Mineral Density in Patients with Type 1 Gaucher Disease in Argentina.

    PubMed

    Larroudé, M S; Aguilar, G; Rossi, I; Drelichman, G; Fernandez Escobar, N; Basack, N; Slago, M; Schenone, A; Fynn, A; Cuello, M F; Fernandez, R; Ruiz, A; Reichel, P; Guelbert, N; Robledo, H; Watman, N; Bolesina, M; Elena, G; Veber, S E; Pujal, G; Galvan, G; Chain, J J; Arizo, A; Bietti, J; Aznar, M; Dragosky, M; Marquez, M; Feldman, L; Muller, K; Zirone, S; Buchovsky, G; Lanza, V; Fernandez, I; Jaureguiberry, R; Barbieri, M A; Maro, A; Zarate, G; Fernandez, G; Rapetti, M; Degano, A; Kantor, G; Albina, A; Alvarez Bollea, M; Arrocena, H; Bacciedoni, V; Del Rio, F

    2016-10-01

    The purpose of this study was to evaluate the frequency of osteoporosis (OP) in patients with Gaucher disease (GD) in Argentina. GD patients from 28 centers were consecutively included from April 2012 to 2014. Bone mineral density (BMD) was determined by dual X-ray absorptiometry in the lumbar spine and the femoral neck or the total proximal femur for patients ≥20 yr of age, and by whole-body scan in the lumbar spine in patients <20 yr of age. In children, mineral density was calculated using the chronological age and Z height. OP diagnosis was determined following adult and pediatric official position of the International Society for Clinical Densitometry. A total of 116 patients were included, of which 62 (53.5%) were women. The median age was 25.8 yr. All patients received enzyme replacement therapy, with a median time of 9.4 yr. Normal BMD was found in 89 patients (76.7%), whereas low bone mass (LBM) or osteopenia was found in 15 patients (13%) and OP in 12 patients (10.3%). The analysis of the pediatric population revealed that 4 patients (9.3%) had LBM and 3 (7%) had OP (Z-score ≤ -2 + fractures height-adjusted by Z), whereas in the adult population (n = 73), 11 patients (15%) had LBM or osteopenia and 9 (12.3%) had OP. Bone marrow infiltration and the presence of fractures were significantly correlated with the presence of OP (p = 0.04 and <0.001, respectively). This is the first study in Argentina and in the region describing the frequency of OP or LBM in GD patients treated with imiglucerase using the official position of the International Society for Clinical Densitometry.

  12. Vitamin D Status and Bone Mineral Density in Obese Children with Nonalcoholic Fatty Liver Disease.

    PubMed

    Chang, Eun Jae; Yi, Dae Yong; Yang, Hye Ran

    2015-12-01

    Whether nonalcoholic fatty liver disease (NAFLD) is related to vitamin D and bone health in obese children is unknown. The aim of this study was to evaluate vitamin D status and bone mineral density (BMD) in obese children according to their condition within the NAFLD spectrum. Anthropometric data, laboratory tests, and abdominal ultrasonography were obtained from 94 obese children. The subjects were divided into three groups according to NAFLD spectrum: normal liver, simple steatosis, and nonalcoholic steatohepatitis (NASH). Although there were no differences in vitamin D levels between the three groups, these groups showed significant differences in highly sensitive C-reactive protein (P=0.044), homeostasis model assessment of insulin resistance (HOMA-IR) (P=0.02), hepatic fibrosis scores (P<0.05), and trunk fat percentage (P=0.025). Although there were significant differences in BMDs, the age-matched BMD z-scores were not significantly different between the three groups. Serum vitamin D levels were negatively correlated with age (r=-0.368, P=0.023), serum uric acid levels (r=-0.371, P=0.022), fibrosis 4 (FIB4) (r=-0.406, P=0.011), and HOMA-IR (r=-0.530, P=0.001) in obese children with NASH. Multiple regression analysis for vitamin D in the NASH group revealed age and HOMA-IR as significant factors. In conclusion, inflammatory markers, hepatic fibrosis scores, trunk fat, and insulin resistance may reflect the spectrum of NAFLD in obese children, whereas vitamin D levels and BMD may not. In patients with NASH, however, low serum vitamin D is associated with hepatic fibrosis and insulin resistance, but not with bone health status.

  13. From "Kidneys Govern Bones" to Chronic Kidney Disease, Diabetes Mellitus, and Metabolic Bone Disorder: A Crosstalk between Traditional Chinese Medicine and Modern Science.

    PubMed

    Wang, Xiao-Qin; Zou, Xin-Rong; Zhang, Yuan Clare

    2016-01-01

    Although traditional Chinese medicine (TCM) and Western medicine have evolved on distinct philosophical foundations and reasoning methods, an increasing body of scientific data has begun to reveal commonalities. Emerging scientific evidence has confirmed the validity and identified the molecular mechanisms of many ancient TCM theories. One example is the concept of "Kidneys Govern Bones." Here we discuss the molecular mechanisms supporting this theory and its potential significance in treating complications of chronic kidney disease (CKD) and diabetes mellitus. Two signaling pathways essential for calcium-phosphate metabolism can mediate the effect of kidneys in bone homeostasis, one requiring renal production of bioactive vitamin D and the other involving an endocrine axis based on kidney-expressed Klotho and bone-secreted fibroblast growth factor 23. Disruption of either pathway can lead to calcium-phosphate imbalance and vascular calcification, accelerating metabolic bone disorder. Chinese herbal medicine is an adjunct therapy widely used for treating CKD and diabetes. Our results demonstrate the therapeutic effects and underlying mechanisms of a Chinese herbal formulation, Shen-An extracts, in diabetic nephropathy and renal osteodystrophy. We believe that the smart combination of Eastern and Western concepts holds great promise for inspiring new ideas and therapies for preventing and treating complications of CKD and diabetes.

  14. Myeloma cell expression of 10 candidate genes for osteolytic bone disease. Only overexpression of DKK1 correlates with clinical bone involvement at diagnosis.

    PubMed

    Haaber, Jacob; Abildgaard, Niels; Knudsen, Lene Meldgaard; Dahl, Inger Marie; Lodahl, Marianne; Thomassen, Mads; Kerndrup, Gitte Birk; Rasmussen, Thomas

    2008-01-01

    Osteolytic bone disease (OBD) in multiple myeloma (MM) is caused by interactions between MM cells and the bone marrow microenvironment and is characterized by increased osteoclastic bone resorption and decreased osteoblastic bone formation. Recently, the role of osteoblast inhibition has come into focus, especially the possible role of overexpression of DKK1, an inhibitor of the Wnt signalling pathway. Further, CKS2, PSME2 and DHFR have also been reported as candidate genes for OBD. We studied the gene expression by quantitative reverse transcription polymerase chain reaction of TNFSF11 (RANKL), TNFSF11A (RANK), TNFRSF11B (OPG), CCL3 (MIP1A), CCL4 (MIP1B), PTHR1 (PTHrp), DKK1, CKS2, PSME2 and DHFR in purified, immunophenotypic FACS-sorted plasma cells from 171 newly diagnosed MM patients, 20 patients with monoclonal gammopathy of undetermined significance and 12 controls. The gene expressions of the analysed genes were correlated with radiographically assessed OBD. Only overexpression of DKK1 was correlated to the degree of OBD. Myeloma cells did not express TNFSF11A, TNFSF11, or TNFRSF11B, and very rarely expressed CCL3 and PTHR11. CCL4, CKS2, PSME2 and DHFR were variably expressed, but the expression of these genes showed no correlation with OBD. In contrast, loss of PSME2 expression in MM plasma cells was significantly correlated with OBD.

  15. Radiographic evaluation of the effect of obesity on alveolar bone in rats with ligature-induced periodontal disease

    PubMed Central

    do Nascimento, Cassiane Merigo; Cassol, Tiago; da Silva, Fernanda Soares; Bonfleur, Maria Lucia; Nassar, Carlos Augusto; Nassar, Patricia Oehlmeyer

    2013-01-01

    There is evidence that the lack of metabolic control of obese patients may accelerate periodontitis. The aim of this study was to evaluate radiographically the effect of cafeteria-diet-induced obesity on alveolar bone loss in rats subjected to periodontal disease. Twenty male Wistar rats were randomly divided into four groups: 1) control group, 2) control and ligature group; 3) cafeteria group; and 4) cafeteria and ligature group. The animals were evaluated for obesity and euthanized, and the mandible of each rat was removed to perform a radiographic evaluation of alveolar bone loss and its effect on diet-induced obesity. The results showed greater alveolar bone loss in the mice in Group 4 (P<0.01). Thus, we concluded that obese mice, on average, showed greater radiographic evidence of alveolar bone loss than mice undergoing induction of obesity. PMID:24124386

  16. Association of Serum Osteoprotegerin Levels with Bone Loss in Chronic Kidney Disease: Insights from the KNOW-CKD Study

    PubMed Central

    Kim, Chang Seong; Bae, Eun Hui; Ma, Seong Kwon; Han, Seung Hyeok; Choi, Kyu Hun; Lee, Joongyub; Chae, Dong Wan; Oh, Kook-Hwan; Ahn, Curie; Kim, Soo Wan

    2016-01-01

    Osteoprotegerin, a potent osteoclast activation inhibitor, decreases bone resorption and positively affects bone mineral density. This study examined the association between serum osteoprotegerin levels and bone loss in patients with chronic kidney disease, a condition associated with increased risk of mineral and bone disorders. The bone mineral densities of the lumbar spine, total hip, and femur neck were assessed by dual-energy X-ray absorptiometry; serum osteoprotegerin levels were measured at baseline for 1,423 patients enrolled in the prospective KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD). Patients aged ≥50 years and with a T-score ≤ –2.5 were diagnosed as having osteoporosis. Multivariable linear regression analysis indicated independent association between serum osteoprotegerin levels and decreased bone mineral density in the lumbar spine (B: –0.489, 95% confidence interval [CI]: –0.883 to –0.095, P = 0.015), and total hip (B: –0.349, 95% CI: –0.672 to –0.027, P = 0.027). However, bone mineral density of the femur neck was not associated with serum osteoprotegerin levels in women. After adjustments, no independent association was found between serum osteoprotegerin levels and bone mineral density in men. In multivariable logistic regression analysis, serum osteoprotegerin levels were associated with increased risk of osteoporosis in women (odds ratio [OR]: 4.72, 95% CI: 1.35 to 16.52, P = 0.015), but not in men (OR: 0.21; 95% CI: 0.04 to 1.31, P = 0.095). To summarize, in female patients with chronic kidney disease, increased serum osteoprotegerin levels were independently associated with decreased bone mineral density in the lumbar spine and total hip, and with increased risk of osteoporosis. Therefore, the measurement of serum osteoprotegerin concentration might be useful as a surrogate marker for determining bone loss in patients with chronic kidney disease, especially for women, although not so

  17. Eradication of bone marrow minimal residual disease may prompt early treatment discontinuation in CLL.

    PubMed

    Strati, Paolo; Keating, Michael J; O'Brien, Susan M; Burger, Jan; Ferrajoli, Alessandra; Jain, Nitin; Tambaro, Francesco Paolo; Estrov, Zeev; Jorgensen, Jeffrey; Challagundla, Pramoda; Faderl, Stefan H; Wierda, William G

    2014-06-12

    The high complete remission rate with first-line combined fludarabine, cyclophosphamide, and rituximab (FCR) begs the question of the value of minimal residual disease (MRD)-negative status as a treatment end point. We report on 237 patients with chronic lymphocytic leukemia who received first-line FCR. MRD was prospectively assessed by 4-color flow cytometry in bone marrow after course 3 and at final response assessment. After course 3 and at final response assessment, 17% and 43% of patients were MRD negative in bone marrow, respectively. A mutated immunoglobulin heavy chain variable gene and trisomy 12 were independently associated with MRD-negative status both after 3 courses of FCR and at final response assessment in multivariable analyses (MVAs). MRD-negative status was independently associated with significantly longer progression-free survival (PFS) and overall survival (OS) in MVA (P = .03 and .02, respectively). This association was confirmed also on landmark MVA at the time of MRD assessment (P = .04 and .05, respectively). MRD-negative patients had comparable PFS and OS, independent of the number of courses received or interim staging. Early MRD eradication may be a desirable goal, prompting consideration of early discontinuation of treatment. This trial was registered at www.clinicaltrials.gov as #NCT00759798.

  18. Eradication of bone marrow minimal residual disease may prompt early treatment discontinuation in CLL

    PubMed Central

    Strati, Paolo; Keating, Michael J.; O'Brien, Susan M.; Burger, Jan; Ferrajoli, Alessandra; Jain, Nitin; Tambaro, Francesco Paolo; Estrov, Zeev; Jorgensen, Jeffrey; Challagundla, Pramoda; Faderl, Stefan H.

    2014-01-01

    The high complete remission rate with first-line combined fludarabine, cyclophosphamide, and rituximab (FCR) begs the question of the value of minimal residual disease (MRD)–negative status as a treatment end point. We report on 237 patients with chronic lymphocytic leukemia who received first-line FCR. MRD was prospectively assessed by 4-color flow cytometry in bone marrow after course 3 and at final response assessment. After course 3 and at final response assessment, 17% and 43% of patients were MRD negative in bone marrow, respectively. A mutated immunoglobulin heavy chain variable gene and trisomy 12 were independently associated with MRD-negative status both after 3 courses of FCR and at final response assessment in multivariable analyses (MVAs). MRD-negative status was independently associated with significantly longer progression-free survival (PFS) and overall survival (OS) in MVA (P = .03 and .02, respectively). This association was confirmed also on landmark MVA at the time of MRD assessment (P = .04 and .05, respectively). MRD-negative patients had comparable PFS and OS, independent of the number of courses received or interim staging. Early MRD eradication may be a desirable goal, prompting consideration of early discontinuation of treatment. This trial was registered at www.clinicaltrials.gov as #NCT00759798. PMID:24705492

  19. Molecular Imaging of Bone Marrow Mononuclear Cell Survival and Homing in Murine Peripheral Artery Disease

    PubMed Central

    van der Bogt, Koen E.A.; Hellingman, Alwine A.; Lijkwan, Maarten A.; Bos, Ernst-Jan; de Vries, Margreet R.; Fischbein, Michael P.; Quax, Paul H.; Robbins, Robert C.; Hamming, Jaap F.; Wu, Joseph C.

    2013-01-01

    Introduction Bone marrow mononuclear cell (MNC) therapy is a promising treatment for peripheral artery disease (PAD). This study aims to provide insight into cellular kinetics using molecular imaging following different transplantation methods. Methods and Results MNCs were isolated from F6 transgenic mice (FVB background) that express firefly luciferase (Fluc) and green fluorescence protein (GFP). Male FVB and C57Bl6 mice (n=50) underwent femoral artery ligation and were randomized into 4 groups receiving: (1) single intramuscular (i.m.) injection of 2×106 MNC; (2) four weekly i.m. injections of 5×105 MNC; (3) 2×106 MNCs intravenously (i.v.); and (4) PBS. Cellular kinetics, measured by in vivo bioluminescence imaging (BLI), revealed near-complete donor cell death 4 weeks after i.m. transplantation. Following i.v. transplantation, BLI monitored cells homed in on the injured area in the limb, as well as to the liver, spleen, and bone marrow. Ex vivo BLI showed presence of MNCs in the scar tissue and adductor muscle. However, no significant effects on neovascularisation were observed as monitored by Laser-Doppler-Perfusion-Imaging and histology. Conclusion This is one of the first studies to assess kinetics of transplanted MNCs in PAD using in vivo molecular imaging. MNC survival is short lived and MNCs do not significantly stimulate perfusion in this model. PMID:22239892

  20. Denosumab for the management of bone disease in patients with solid tumors.

    PubMed

    Body, Jean-Jacques

    2012-03-01

    Many patients with advanced cancer develop bone metastases, which reduces their quality of life. Bone metastases are associated with an increased risk of skeletal-related events, which can lead to increased morbidity and mortality. In patients with bone metastases, tumor cells disrupt the normal process of bone remodeling, leading to increased bone destruction. Denosumab is a fully human monoclonal antibody against receptor activator of NF-κB ligand (RANKL), a key regulatory factor in bone remodeling. By binding to RANKL, denosumab disrupts the cycle of bone destruction. In clinical studies in patients with prostate or breast cancer and bone metastases, denosumab was superior to the current standard of care, zoledronic acid, for delaying skeletal-related events, while in patients with other solid tumors or multiple myeloma, denosumab was noninferior to zoledronic acid. This article examines the pharmacokinetics, efficacy, and safety and tolerability of denosumab for the management of bone events in patients with cancer.

  1. Osteoblast CFTR inactivation reduces differentiation and osteoprotegerin expression in a mouse model of cystic fibrosis-related bone disease.

    PubMed

    Stalvey, Michael S; Clines, Katrina L; Havasi, Viktoria; McKibbin, Christopher R; Dunn, Lauren K; Chung, W Joon; Clines, Gregory A

    2013-01-01

    Low bone mass and increased fracture risk are recognized complications of cystic fibrosis (CF). CF-related bone disease (CFBD) is characterized by uncoupled bone turnover--impaired osteoblastic bone formation and enhanced osteoclastic bone resorption. Intestinal malabsorption, vitamin D deficiency and inflammatory cytokines contribute to CFBD. However, epidemiological investigations and animal models also support a direct causal link between inactivation of skeletal cystic fibrosis transmembrane regulator (CFTR), the gene that when mutated causes CF, and CFBD. The objective of this study was to examine the direct actions of CFTR on bone. Expression analyses revealed that CFTR mRNA and protein were expressed in murine osteoblasts, but not in osteoclasts. Functional studies were then performed to investigate the direct actions of CFTR on osteoblasts using a CFTR knockout (Cftr-/-) mouse model. In the murine calvarial organ culture assay, Cftr-/- calvariae displayed significantly less bone formation and osteoblast numbers than calvariae harvested from wildtype (Cftr+/+) littermates. CFTR inactivation also reduced alkaline phosphatase expression in cultured murine calvarial osteoblasts. Although CFTR was not expressed in murine osteoclasts, significantly more osteoclasts formed in Cftr-/- compared to Cftr+/+ bone marrow cultures. Indirect regulation of osteoclastogenesis by the osteoblast through RANK/RANKL/OPG signaling was next examined. Although no difference in receptor activator of NF-κB ligand (Rankl) mRNA was detected, significantly less osteoprotegerin (Opg) was expressed in Cftr-/- compared to Cftr+/+ osteoblasts. Together, the Rankl:Opg ratio was significantly higher in Cftr-/- murine calvarial osteoblasts contributing to a higher osteoclastogenesis potential. The combined findings of reduced osteoblast differentiation and lower Opg expression suggested a possible defect in canonical Wnt signaling. In fact, Wnt3a and PTH-stimulated canonical Wnt signaling

  2. Fluid-driven fractures in brittle hydrogels

    NASA Astrophysics Data System (ADS)

    O'Keeffe, Niall; Linden, Paul

    2016-11-01

    Hydraulic fracturing is a process in which fluid is injected deep underground at high pressures that can overcome the strength of the surrounding matrix. This results in an increase of surface area connected to the well bore and thus allows extraction of natural gas previously trapped in a rock formation. We experimentally study the physical mechanisms of these fluid-driven fractures in low permeability reservoirs where the leak-off of fracturing fluid is considered negligible. This is done through the use of small scale experiments on transparent and brittle, heavily cross-linked hydrogels. The propagation of these fractures can be split into two distinct regimes depending on whether the dominant energy dissipation mechanism is viscous flow or material toughness. We will analyse crack growth rates, crack thickness and tip shape in both regimes. Moreover, PIV techniques allow us to explore the flow dynamics within the fracture, which is crucial in predicting transport of proppants designed to prevent localisation of cracks.

  3. Brittle to ductile transition in cleavage fracture

    SciTech Connect

    Argon, A.S.; Berg, Q.

    1992-09-30

    The problem of interpretation of fracture transition from brittle to ductile or vice versa is the subject of study. An instrumented tapered double cantilever beam (TDCB) has been developed as a definitive tool in the study of the intrinsic mechanism in single crystalline samples. In this experiment, the crack velocity is directly proportional to actuator velocity. In experiments performed on TDCB shaped Si single crystals, oriented for cleavage on either [l brace]111[r brace] or [l brace]110[r brace] planes, a number of troubling features of jerky carck extension were encountered. Evidence suggests that nucleation of dislocation loops from crack tip is easier than moving these dislocations away from crack tip. 14 refs, 1 fig.

  4. Isotropic MD simulations of dynamic brittle fracture

    SciTech Connect

    Espanol, P.; Rubio, M.A.; Zuniga, I.

    1996-12-01

    The authors present results obtained by molecular dynamics simulations on the propagation of fast cracks in triangular 2D lattices. Their aim is to simulate Mode 1 fracture of brittle isotropic materials. They propose a force law that respects the isotropy of the material. The code yields the correct imposed sound c{sub {parallel}}, shear c{sub {perpendicular}} and surface V{sub R} wave speeds. Different notch lengths are systematically studied. They observed that initially the cracks are linear and always branch at a particular critical velocity c* {approx} 0.8V{sub R} and that this occurs when the crack tip reaches the position of a front emitted from the initial crack tip and propagating at a speed c = 0.68V{sub R}.

  5. A probabilistic model of brittle crack formation

    NASA Technical Reports Server (NTRS)

    Chudnovsky, A.; Kunin, B.

    1987-01-01

    Probability of a brittle crack formation in an elastic solid with fluctuating strength is considered. A set Omega of all possible crack trajectories reflecting the fluctuation of the strength field is introduced. The probability P(X) that crack penetration depth exceeds X is expressed as a functional integral over Omega of a conditional probability of the same event taking place along a particular path. Various techniques are considered to evaluate the integral. Under rather nonrestrictive assumptions, the integral is reduced to solving a diffusion-type equation. A new characteristic of fracture process, 'crack diffusion coefficient', is introduced. An illustrative example is then considered where the integration is reduced to solving an ordinary differential equation. The effect of the crack diffusion coefficient and of the magnitude of strength fluctuations on probability density of crack penetration depth is presented. Practical implications of the proposed model are discussed.

  6. Brittle dynamic damage due to earthquake rupture

    NASA Astrophysics Data System (ADS)

    Bhat, Harsha; Thomas, Marion

    2016-04-01

    The micromechanical damage mechanics formulated by Ashby and Sammis, 1990, and generalized by Deshpande and Evans 2008 has been extended to allow for a more generalized stress state and to incorporate an experimentally motivated new crack growth (damage evolution) law that is valid over a wide range of loading rates. This law is sensitive to both the crack tip stress field and its time derivative. Incorporating this feature produces additional strain-rate sensitivity in the constitutive response. The model is also experimentally verified by predicting the failure strength of Dionysus-Pentelicon marble over wide range of strain rates. We then implement this constitutive response to understand the role of dynamic brittle off-fault damage on earthquake ruptures. We show that off-fault damage plays an important role in asymmetry of rupture propagation and is a source of high-frequency ground motion in the near source region.

  7. Bone is Not Alone: the Effects of Skeletal Muscle Dysfunction in Chronic Kidney Disease.

    PubMed

    Avin, Keith G; Moorthi, Ranjani N

    2015-06-01

    Chronic kidney disease (CKD) is associated with a decline in muscle mass, strength, and function, collectively called "sarcopenia." Sarcopenia is associated with hospitalizations and mortality in CKD and is therefore important to understand and characterize. While the focus of skeletal health in CKD has traditionally focused on bone and mineral aberrations, it is now recognized that sarcopenia must also play a role in poor musculoskeletal health in this population. In this paper, we present an overview of skeletal muscle changes in CKD, including defects in skeletal muscle catabolism and anabolism in uremic tissue. There are many gaps in knowledge in this field that should be the focus for future research to unravel pathogenesis and therapies for musculoskeletal health in CKD.

  8. Bone disease in patients on maintenance haemodialysis using softened or de-ionized water.

    PubMed

    Hudson, G A; Milne, F J; Oliver, N J; Reis, P; Murray, J; Meyers, A M

    1979-09-08

    A clinical, biochemical and radiological study was carried out in 28 patients on maintenance haemodialysis in order to assess the prevalence of bone disease, particularly with regard to osteomalacia and/or osteopenia. The patients were selected from dialysis units using softened or deionized water, and the aluminium levels measured in the different water supplies. The results showed that symptomatic osteomalacia/osteopenia occurs more frequently in the units using softened water, which has a higher aluminium content, than in the de-ionized water unit. The patients dialysed on softened water also have significantly higher serum calcium and phosphorus levels. It is suggested that in Johannesburg, water softening alone is inadequate, and that the high aluminium levels in our water may be responsible for accelerated osteomalacia/osteopenia.

  9. [Treatment for CKD-MBD(Chronic Kidney Disease-Mineral and Bone Disorder)].

    PubMed

    Iwashita, Yuko; Iwashita, Yu; Ito, Takafumi; Shigematsu, Takashi

    2016-02-01

    CKD is a common disease that is estimated to develop one in eight persons in Japan. The CKD itself is highly risk factor on the cardiac/vascular mortality. In addition,a new concept has been proposed "CKD-MBD". CKD-MBD is composed of a combination of abnormal mineral metabolism, abnormal bone, and extra skeletal calcification with cardiovascular high mortality. Treatment for CKD-MBD is a wide-ranging. We aim to decline cardiovascular event, fracture, and mortality rate of patients with CKD. The main therapeutic target for CKD-MBD becomes the phosphate control. Today, we can use of the VRDA, Calcimimetics and muti-phosphate binders as a lot of pharmacological intervention.

  10. Targeting the Molecular and Cellular Interactions of the Bone Marrow Niche in Immunologic Disease

    PubMed Central

    Brozowski, Jaime M.; Billard, Matthew J.

    2014-01-01

    Recent investigations have expanded our knowledge of the regulatory bone marrow (BM) niche, which is critical in maintaining and directing hematopoietic stem cell (HSC) self-renewal and differentiation. Osteoblasts, mesenchymal stem cells (MSCs), and CXCL12-abundant reticular (CAR) cells are niche components in close association with HSCs and have been more clearly defined in immune cell function and homeostasis. Importantly, cellular inhabitants of the BM niche signal through G protein-coupled surface receptors (GPCRs) for various appropriate immune functions. In this article, recent literature on BM niche inhabitants (HSCs, osteoblasts, MSCs, CAR cells) and their GPCR mechanistic interactions are reviewed for better understanding of the BM cells involved in immune development, immunologic disease, and current immune reconstitution therapies. PMID:24408534

  11. XBONE: a hybrid expert system for supporting diagnosis of bone diseases.

    PubMed

    Hatzilygeroudis, I; Vassilakos, P J; Tsakalidis, A

    1997-01-01

    In this paper, XBONE, a hybrid medical expert system that supports diagnosis of bone diseases is presented. Diagnosis is based on various patient data and is performed in two stages. In the early stage, diagnosis is based on demographic and clinical data of the patient, whereas in the late stage it is mainly based on nuclear medicine image data. Knowledge is represented via an integrated formalism that combines production rules and the Adaline artificial neural unit. Each condition of a rule is assigned a number, called its significance factor, representing its significance in drawing the conclusion of the rule. This results in better representation, reduction of the knowledge base size and gives the system learning capabilities.

  12. Benchmarking numerical models of brittle thrust wedges

    NASA Astrophysics Data System (ADS)

    Buiter, Susanne J. H.; Schreurs, Guido; Albertz, Markus; Gerya, Taras V.; Kaus, Boris; Landry, Walter; le Pourhiet, Laetitia; Mishin, Yury; Egholm, David L.; Cooke, Michele; Maillot, Bertrand; Thieulot, Cedric; Crook, Tony; May, Dave; Souloumiac, Pauline; Beaumont, Christopher

    2016-11-01

    We report quantitative results from three brittle thrust wedge experiments, comparing numerical results directly with each other and with corresponding analogue results. We first test whether the participating codes reproduce predictions from analytical critical taper theory. Eleven codes pass the stable wedge test, showing negligible internal deformation and maintaining the initial surface slope upon horizontal translation over a frictional interface. Eight codes participated in the unstable wedge test that examines the evolution of a wedge by thrust formation from a subcritical state to the critical taper geometry. The critical taper is recovered, but the models show two deformation modes characterised by either mainly forward dipping thrusts or a series of thrust pop-ups. We speculate that the two modes are caused by differences in effective basal boundary friction related to different algorithms for modelling boundary friction. The third experiment examines stacking of forward thrusts that are translated upward along a backward thrust. The results of the seven codes that run this experiment show variability in deformation style, number of thrusts, thrust dip angles and surface slope. Overall, our experiments show that numerical models run with different numerical techniques can successfully simulate laboratory brittle thrust wedge models at the cm-scale. In more detail, however, we find that it is challenging to reproduce sandbox-type setups numerically, because of frictional boundary conditions and velocity discontinuities. We recommend that future numerical-analogue comparisons use simple boundary conditions and that the numerical Earth Science community defines a plasticity test to resolve the variability in model shear zones.

  13. Is Coronary Artery Calcification Associated with Vertebral Bone Density in Nondialyzed Chronic Kidney Disease Patients?

    PubMed Central

    Filgueira, Agostinho; Carvalho, Aluizio Barbosa; Tomiyama, Cristiane; Higa, Andrea; Rochitte, Carlos E.; Santos, Raul D.

    2011-01-01

    Summary Background and objectives Low bone mineral density and coronary artery calcification (CAC) are highly prevalent among chronic kidney disease (CKD) patients, and both conditions are strongly associated with higher mortality. The study presented here aimed to investigate whether reduced vertebral bone density (VBD) was associated with the presence of CAC in the earlier stages of CKD. Design, setting, participants, & measurements Seventy-two nondialyzed CKD patients (age 52 ± 11.7 years, 70% male, 42% diabetics, creatinine clearance 40.4 ± 18.2 ml/min per 1.73 m2) were studied. VBD and CAC were quantified by computed tomography. Results CAC > 10 Agatston units (AU) was observed in 50% of the patients (median 120 AU [interquartile range 32 to 584 AU]), and a calcification score ≥ 400 AU was found in 19% (736 [527 to 1012] AU). VBD (190 ± 52 Hounsfield units) correlated inversely with age (r = −0.41, P < 0.001) and calcium score (r = −0.31, P = 0.01), and no correlation was found with gender, creatinine clearance, proteinuria, lipid profile, mineral parameters, body mass index, and diabetes. Patients in the lowest tertile of VBD had expressively increased calcium score in comparison to the middle and highest tertile groups. In the multiple logistic regression analysis adjusting for confounding variables, low VBD was independently associated with the presence of CAC. Conclusions Low VBD was associated with CAC in nondialyzed CKD patients. The authors suggest that low VBD might constitute another nontraditional risk factor for cardiovascular disease in CKD. PMID:21617086

  14. Clinical Studies in Familial VCP Myopathy Associated With Paget Disease of Bone and Frontotemporal Dementia

    PubMed Central

    Kimonis, Virginia. E.; Mehta, Sarju G.; Fulchiero, Erin C.; Thomasova, Dana; Pasquali, Marzia; Boycott, Kym; Neilan, Edward G.; Kartashov, Alex; Forman, Mark S.; Tucker, Stuart; Kimonis, Katerina; Mumm, Steven; Whyte, Michael P.; Smith, Charles D.; Watts, Giles D. J.

    2008-01-01

    Inclusion body myopathy with Paget disease of the bone (PDB) and/or frontotemporal dementia (IBMPFD, OMIM 167320), is a progressive autosomal dominant disorder caused by mutations in the Valousin-containing protein (VCP, p97 or CDC48) gene. IBMPFD can be difficult to diagnose. We assembled data on a large set of families to illustrate the number and type of misdiagnoses that occurred. Clinical analysis of 49 affected individuals in nine families indicated that 42 (87%) of individuals had muscle disease. The majority were erroneously diagnosed with limb girdle muscular dystrophy (LGMD), facioscapular muscular dystrophy, peroneal muscular dystrophy, late adult onset distal myopathy, spinal muscular atrophy, scapuloperoneal muscular dystrophy, or amyotrophic lateral sclerosis (ALS) among others. Muscle biopsies showed rimmed vacuoles characteristic of an inclusion body myopathy in 7 of 18 patients (39%), however, inclusion body myopathy was correctly diagnosed among individuals in only families 5 and 15. Frontotemporal dementia (FTD) was diagnosed in 13 individuals (27%) at a mean age of 57 years (range 48.9–60.2 years); however, several individuals had been diagnosed with Alzheimer disease. Histopathological examination of brains of three affected individuals revealed a pattern of ubiquitin positive neuronal intranuclear inclusions and dystrophic neurites. These families expand the clinical phenotype in IBMPFD, a complex disorder caused by mutations in VCP. The presence of PDB in 28 (57%) individuals suggests that measuring serum alkaline phosphatase (ALP) activity may be a useful screen for IBMPFD in patients with myopathy. PMID:18260132

  15. Neuroprotective properties of the innate immune system and bone marrow stem cells in Alzheimer's disease.

    PubMed

    Simard, A R; Rivest, S

    2006-04-01

    The role of innate immunity and microglia in the brain is currently a matter of great debate and controversy. While several studies have provided evidence that they contribute to neurodegeneration in various animal models of brain diseases and traumas, others have shown that their inhibition may in contrast be associated with more damages or less repair. We have recently reported the existence of two different types of microglia, the resident and the newly differentiated microglia that derive from the bone marrow stem cells. Of great interest is the fact that blood-derived microglial cells are associated with amyloid plaques and these cells are able to prevent the formation or eliminate the presence of amyloid deposits in mice that develop the major hallmark of Alzheimer's disease (AD). These newly recruited cells are specifically attracted to the beta-amyloid 40/42 isoforms in vivo and they participate in the elimination of these proteins by phagocytosis. This review presents the mechanisms involved in the control of the innate immune response by microglia and the beneficial properties of such a response in brain diseases, such as AD.

  16. Bone marrow transplantation prolongs life span and ameliorates neurologic manifestations in Sandhoff disease mice.

    PubMed Central

    Norflus, F; Tifft, C J; McDonald, M P; Goldstein, G; Crawley, J N; Hoffmann, A; Sandhoff, K; Suzuki, K; Proia, R L

    1998-01-01

    The GM2 gangliosidoses are a group of severe, neurodegenerative conditions that include Tay-Sachs disease, Sandhoff disease, and the GM2 activator deficiency. Bone marrow transplantation (BMT) was examined as a potential treatment for these disorders using a Sandhoff disease mouse model. BMT extended the life span of these mice from approximately 4.5 mo to up to 8 mo and slowed their neurologic deterioration. BMT also corrected biochemical deficiencies in somatic tissues as indicated by decreased excretion of urinary oligosaccharides, and lower glycolipid storage and increased levels of beta-hexosaminidase activity in visceral organs. Even with neurologic improvement, neither clear reduction of brain glycolipid storage nor improvement in neuronal pathology could be detected, suggesting a complex pathogenic mechanism. Histological analysis revealed beta-hexosaminidase-positive cells in the central nervous system and visceral organs with a concomitant reduction of colloidal iron-positive macrophages. These results may be important for the design of treatment approaches for the GM2 gangliosidoses. PMID:9576752

  17. Potential of bone marrow mesenchymal stem cells in management of Alzheimer's disease in female rats.

    PubMed

    Salem, Ahmed M; Ahmed, Hanaa H; Atta, Hazem M; Ghazy, Mohamed A; Aglan, Hadeer A

    2014-12-01

    Alzheimer's disease (AD) has been called the disease of the century with significant clinical and socioeconomic impacts. Pharmacological treatment has limited efficacy and only provides symptomatic relief without long-term cure. Accordingly, there is an urgent need to develop novel and effective medications for AD. Stem cell-based therapy is a promising approach to handling neurodegenerative diseases. Therefore, the current study aimed to explore the possible therapeutic role of single intravenous injection of bone marrow derived mesenchymal stem cells (BM-MSCs) after 4 months in management of AD in the experimental model. The work also extended to compare the therapeutic potential of BM-MSCs with 2 conventional therapies of AD; rivastigmine and cerebrolysin administered daily. BM-MSCs were able to home at the injured brains and produced significant increases in the number of positive cells for choline acetyltransferase (ChAT) and survivin expression, as well as selective AD indicator-1 (seladin-1) and nestin gene expression. Histopathological examination indicated that BM-MSCs could remove beta-amyloid plaques from hippocampus. Significant improvement in these biomarkers was similar to or better sometimes than the reference drugs, clearly showing the potential therapeutic role of BM-MSCs against AD through their anti-apoptotic, neurogenic and immunomodulatory properties.

  18. Bone scintigraphy as cornerstone in the diagnosis of Erdheim-Chester disease.

    PubMed

    García-Gómez, F J; Cambil-Molina, T; Ríos-Martín, J J; de la Riva-Pérez, P A; Calvo-Morón, C; Castro-Montaño, J

    2016-01-01

    The Erdheim-Chester disease (ECD) is an extremely rare form of non-Langerhans cell histiocytosis. The main difficulty for its diagnosis lies in the wide variety of non-specific symptoms and signs that can occur in the disease process, leading, therefore, to there being no clear-cut algorithm as a guide for an optimal biopsy to confirm the diagnosis. An 81-year-old male with history of diabetes insipidus was admitted due to non-specific respiratory signs. Imaging techniques revealed osteoblastic lesions in the lumbar spine. Whole-body bone-scintigraphy (BS) was performed, in which lesions involving the axial and appendicular skeleton, with different rates of osteoblastic activity, were observed. This highlighted a symmetrical severely intense uptake in the knees, leading to an accurate biopsy specimen that enabled making the definitive diagnosis. BS is a widely available, safe, and inexpensive technique that shows a characteristic pattern of uptake for ECD, thus its use is highly recommended for screening and guiding biopsy if clinical suspicion exists. Furthermore, when the scintigraphy pattern is incidentally observed, biopsy of increased uptake areas (tibia preferably) is mandatory in order to rule out the disease.

  19. Type 2B von Willebrand disease associated with the release of platelet agglutinates from megakaryocytes in the bone marrow.

    PubMed

    Slayton, William B; Patel, Milin; Sola-Visner, Martha; Harris, Neil; Rivers, Angela; Montgomery, Robert R; Friedman, Kenneth D

    2008-09-01

    We report a child with thrombocytopenia since birth, circulating platelet agglutinates, and a tendency to bleed. A bone marrow aspirate revealed large platelet clumps within the bone marrow and megakaryocyte nuclei surrounded by halos of clumped platelets. Laboratory evaluation revealed type 2B von Willebrand disease. Gene sequencing revealed a G to C mutation at base 3923 of the VWF gene. This mutation was previously described in a family with circulating platelet clumps and abnormal megakaryopoiesis with release of clumped platelets in culture. This same mutation was previously described in a family with circulating platelet aggregates and abnormalities of platelet release from megakaryocytes in vitro. Presence of megakaryocytes with halos of clumped platelets in our patient suggests that platelet agglutinate occurs in the bone marrow in some type 2B von Willebrand disease patients.

  20. Increased incidence of murine graft-versus-host disease after allogeneic bone marrow transplantation by previous infusion of syngeneic bone marrow cells

    SciTech Connect

    Waer, M.; Ang, K.K.; van der Schueren, E.; Vandeputte, M.

    1984-10-01

    Different groups of BALB/c mice received supralethal total-body irradiation (TBI; 8.5 Gy, day 0). When 30 x 10(6) allogeneic (C57B1) bone marrow (BM) cells were infused with or without 10 x 10(6) syngeneic (BALB/c) bM cells on day 1, many animals (60%) died from graft-versus-host disease (GVHD). Typing of peripheral blood leukocytes for donor antigens showed that, respectively, 22/22 and 17/21 of the mice in both groups became chimeric. When syngeneic bone marrow was given on day 1 and allogeneic bone marrow on day 2 after TBI, a similar number of animals (21/23) became chimeric, but GVHD occurred more frequently in this group (25/26 mice, P less than 0.01). When the syngeneic bone marrow cells were replaced by spleen cells, or when the transplantation of allogeneic bone marrow was delayed till days 3 or 6 after TBI, almost all mice rejected the allogeneic BM graft and became long-term survivors. BALB/c mice receiving 30 x 10(6) C57B1 BM cells after 17 daily fractions of 0.2 Gy of total lymphoid irradiation (TLI), showed a high incidence of chimerism (15/17) and in none of the latter animals was GVHD observed. Despite the high incidence of GVHD in the mice receiving allogeneic BM after TBI and syngeneic BM transplantation, as compared with mice prepared with TLI which do not develop GVHD, suppressor cells were as easily induced after TBI and syngeneic BM transplantation as after TLI.

  1. [Bone and calcium update; diagnosis and therapy of metabolic bone disease update. Advances in clinical trials for osteoporosis in Japan].

    PubMed

    Nakamura, Toshitaka

    2011-12-01

    Microdensitometry of the metacarpal bone on radiograph was first set up as the endpoint of the treatment in clinical trials in Japan in 1980s. Then, radial bone mineral content obtained by single photon absorptiometry was used. In 1990s, lumbar spine BMD measured by DXA became the major endpoint of the study which was designed as prospective, randomized, double-blind, controlled trial. In 2000s, assessments on the incidences of the vertebral fractures have become mandatory as the primary endpoint of the placebo-controlled trial. The numbers of the subjects required in the study are getting larger and the subtleties in the study including adverse events more important along the progress of evidence-based medicine.

  2. Bone loss in patients with untreated chronic obstructive pulmonary disease is mediated by an increase in bone resorption associated with hypercapnia.

    PubMed

    Dimai, H P; Domej, W; Leb, G; Lau, K H

    2001-11-01

    This study sought to determine whether the bone loss in untreated chronic obstructive pulmonary disease (COPD) is associated with hypercapnia and/or respiratory acidosis. Bone mineral density (BMD) measured at the distal forearm of the nondominant arm (with peripheral quantitative computed tomography [pQCT]) and serum markers of bone turnover were determined in 71 male patients with untreated COPD and 40 healthy male subjects who matched the patients in age, weight, and body mass index (BMI). The COPD patients, compared with controls, had reduced pulmonary functions, lower arterial pH, and elevated arterial partial pressure of CO2 (PCO2) The BMD (in T score) was significantly lower in COPD patients than that in control subjects (-1.628 +/- 0.168 vs. -0.058 +/- 0.157; p < 0.001). The BMD of COPD patients correlated positively with arterial pH (r = 0.582; p < 0.001), negatively with PCO2 (r = -0.442; p < 0.001), and negatively with serum cross-linked telopeptide of type I collagen (ICTP), a bone resorption marker (r = -0.444; p < 0.001) but not with serum osteocalcin, a bone formation marker. Serum ICTP, but not osteocalcin, correlated with PCO2 (r = 0.593; p < 0.001) and arterial pH (r = -0.415; p < 0.001). To assess the role of hypercapnia, COPD patients were divided into the hypercapnic (PCO2 > 45 mm Hg; n = 35) and eucapnic (PCO2 = 35-45 mm Hg) group (n = 36). Patients with hypercapnia had lower BMD, lower arterial pH, and higher serum ICTP than did patients with eucapnia. Arterial pH and serum ICTP of eucapnic patients were not different from those of controls. To evaluate the role of uncompensated respiratory acidosis, COPD patients with hypercapnia were subdivided into those with compensatory respiratory acidosis (pH > or = 7.35; n = 20) and those with uncompensated respiratory acidosis (pH < 7.35; n = 15). The BMD and serum ICTP were not different among the two subgroups. In conclusion, this study presents the first associative evidence that the bone loss in

  3. Feeding flaxseed oil but not secoisolariciresinol diglucoside results in higher bone mass in healthy rats and rats with kidney disease.

    PubMed

    Weiler, H A; Kovacs, H; Nitschmann, E; Bankovic-Calic, N; Aukema, H; Ogborn, M

    2007-05-01

    Flaxseed's oil and lignan, secoisolariciresinol diglucoside (SDG), are implicated in attainment of health and treatment of renal injury and osteoporosis. To test for these benefits, weanling Han:SPRD-cy rats (n=171) with or without kidney disease were randomized to diets made with either corn oil or flaxseed oil and with or without SDG for 12 weeks. In females, weight was lower with the SDG diet. In males fed flaxseed oil, lean mass was higher and fat % was lower. In both sexes, fat % was lower in diseased rats. Bone mineral content (BMC) and density were higher in rats fed flaxseed oil and lower in diseased rats, additionally; BMC was lower in SDG-supplemented females. The benefit of flaxseed oil on body composition is sex specific but the effect on bone mass is not. Lastly, reduced weight due to early rat kidney disease is not due to loss of lean body mass.

  4. Bone Density Test

    MedlinePlus

    Tests and Procedures Bone density test By Mayo Clinic Staff A bone density test determines if you have osteoporosis — a disease that causes bones to ... your bones could be quite weak. A bone density test enhances the accuracy of calculating your risk ...

  5. The role of single-photon emission computed tomography/computed tomography in benign and malignant bone disease.

    PubMed

    Horger, Marius; Bares, Roland

    2006-10-01

    Radiological (plain radiographs, computed tomography [CT], magnetic resonance imaging [MRI]) and nuclear medicine methods (bone scan, leukocyte scan) both provide unique information about the status of the skeleton. Both have typical strengths and weaknesses, which often lead to the sequential use of different procedures in daily routine. This use causes the unnecessary loss of time and sometimes money, if redundant information is obtained without establishing a final diagnosis. Recently, new devices for hybrid imaging (single-photon emission computed tomography/computed tomography [SPECT/CT], positron emission tomography/computed tomography [PET/CT]) were introduced, which allow for direct fusion of morphological (CT) and functional (SPECT, PET) data sets. With regard to skeletal abnormalities, this approach appears to be extremely useful because it combines the advantages of both techniques (high-resolution imaging of bone morphology and high sensitivity imaging of bone metabolism). By the accurate correlation of both, a new quality of bone imaging has now become accessible. Although researchers undertaking the initial studies exclusively used low-dose CT equipment, a new generation of SPECT/CT devices has emerged recently. By integrating high-resolution spiral CT, quality of bone imaging may improve once more. Ongoing prospective studies will have to show whether completely new diagnostic algorithms will come up for classification of bone disease as a consequence of this development. Besides, the role of ultrasonography and MRI for bone and soft-tissue imaging also will have to be re-evaluated. Looking at the final aim of all imaging techniques--to achieve correct diagnosis in a fast, noninvasive, comprehensive, and inexpensive way--we are now on the edge of a new era of multimodality imaging that will probably change the paths and structure of medicine in many ways. Presently, hybrid imaging using SPECT/CT has been proven to increase sensitivity and specificity

  6. A Fatal Case of Immune Hyperhemolysis with Bone Marrow Necrosis in a Patient with Sickle Cell Disease

    PubMed Central

    Singavi, Arun; Johnson, Susan T.; Field, Joshua J.

    2017-01-01

    In patients with sickle cell disease, hyperhemolysis is a rare but life-threatening complication of transfusion. In this case report, we describe a 61 year-old woman with hemoglobin sickle cell (SC) disease and history of alloimmunization who developed hyperhemolysis associated with a transfusion. She was found to have a warm and a clinically-significant cold autoantibody. Severe anemia (Hb 2.7 g/dL) with reticulocytopenia and thrombocytopenia prompted a bone marrow biopsy, which demonstrated extensive bone marrow necrosis. Despite treatment, the bone marrow failure did not improve and the patient died on hospital day 38. This case illustrates the potential risks of transfusion in a patient with sickle cell disease, especially one with previous hemolytic reactions. While uncommon, hyperhemolysis can cause death, in this case by extensive bone marrow necrosis. In patients with sickle cell disease, judicious use of red cell transfusions with phenotypically-matched units can diminish, but never completely abrogate, the risks associated with transfusion. PMID:28286630

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

    PubMed Central

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

    2015-01-01

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

  8. Reference point indentation is not indicative of whole mouse bone measures of stress intensity fracture toughness

    PubMed Central

    Carriero, Alessandra; Bruse, Jan L.; Oldknow, Karla J.; Millán, José Luis; Farquharson, Colin; Shefelbine, Sandra J.

    2014-01-01

    Bone fragility is a concern for aged and diseased bone. Measuring bone toughness and understanding fracture properties of the bone are critical for predicting fracture risk associated with age and disease and for preclinical testing of therapies. A reference point indentation technique (BioDent) has recently been developed to determine bone's resistance to fracture in a minimally invasive way by measuring the indentation distance increase (IDI) between the first and last indentations over cyclic indentations in the same position. In this study, we investigate the relationship between fracture toughness KC and reference point indentation parameters (i.e. IDI, total indentation distance (TID) and creep indentation distance (CID)) in bones from 38 mice from six types (C57Bl/6, Balb, oim/oim, oim/+, Phospho1−/− and Phospho1 wild type counterpart). These mice bone are models of healthy and diseased bone spanning a range of fracture toughness from very brittle (oim/oim) to ductile (Phospho1−/−). Left femora were dissected, notched and tested in 3-point bending until complete failure. Contralateral femora were dissected and indented in 10 sites of their anterior and posterior shaft surface over 10 indentation cycles. IDI, TID and CID were measured. Results from this study suggest that reference point indentation parameters are not indicative of stress intensity fracture toughness in mouse bone. In particular, the IDI values at the anterior mid-diaphysis across mouse types overlapped, making it difficult to discern differences between mouse types, despite having extreme differences in stress intensity based toughness measures. When more locations of indentation were considered, the normalised IDIs could distinguish between mouse types. Future studies should investigate the relationship of the reference point indentation parameters for mouse bone in other material properties of the bone tissue in order to determine their use for measuring bone quality. PMID:25280470

  9. Reference point indentation is not indicative of whole mouse bone measures of stress intensity fracture toughness.

    PubMed

    Carriero, Alessandra; Bruse, Jan L; Oldknow, Karla J; Millán, José Luis; Farquharson, Colin; Shefelbine, Sandra J

    2014-12-01

    Bone fragility is a concern for aged and diseased bone. Measuring bone toughness and understanding fracture properties of the bone are critical for predicting fracture risk associated with age and disease and for preclinical testing of therapies. A reference point indentation technique (BioDent) has recently been developed to determine bone's resistance to fracture in a minimally invasive way by measuring the indentation distance increase (IDI) between the first and last indentations over cyclic indentations in the same position. In this study, we investigate the relationship between fracture toughness KC and reference point indentation parameters (i.e. IDI, total indentation distance (TID) and creep indentation distance (CID)) in bones from 38 mice from six types (C57Bl/6, Balb, oim/oim, oim/+, Phospho1(-/-) and Phospho1 wild type counterpart). These mice bone are models of healthy and diseased bone spanning a range of fracture toughness from very brittle (oim/oim) to ductile (Phospho1(-/-)). Left femora were dissected, notched and tested in 3-point bending until complete failure. Contralateral femora were dissected and indented in 10 sites of their anterior and posterior shaft surface over 10 indentation cycles. IDI, TID and CID were measured. Results from this study suggest that reference point indentation parameters are not indicative of stress intensity fracture toughness in mouse bone. In particular, the IDI values at the anterior mid-diaphysis across mouse types overlapped, making it difficult to discern differences between mouse types, despite having extreme differences in stress intensity based toughness measures. When more locations of indentation were considered, the normalised IDIs could distinguish between mouse types. Future studies should investigate the relationship of the reference point indentation parameters for mouse bone in other material properties of the bone tissue in order to determine their use for measuring bone quality.

  10. NF-κB as a Therapeutic Target in Inflammatory-Associated Bone Diseases.

    PubMed

    Lin, T-H; Pajarinen, J; Lu, L; Nabeshima, A; Cordova, L A; Yao, Z; Goodman, S B

    2017-01-01

    Inflammation is a defensive mechanism for pathogen clearance and maintaining tissue homeostasis. In the skeletal system, inflammation is closely associated with many bone disorders including fractures, nonunions, periprosthetic osteolysis (bone loss around orthopedic implants), and osteoporosis. Acute inflammation is a critical step for proper bone-healing and bone-remodeling processes. On the other hand, chronic inflammation with excessive proinflammatory cytokines disrupts the balance of skeletal homeostasis involving osteoblastic (bone formation) and osteoclastic (bone resorption) activities. NF-κB is a transcriptional factor that regulates the inflammatory response and bone-remodeling processes in both bone-forming and bone-resorption cells. In vitro and in vivo evidences suggest that NF-κB is an important potential therapeutic target for inflammation-associated bone disorders by modulating inflammation and bone-remodeling process simultaneously. The challenges of NF-κB-targeting therapy in bone disorders include: (1) the complexity of canonical and noncanonical NF-κB pathways; (2) the fundamental roles of NF-κB-mediated signaling for bone regeneration at earlier phases of tissue damage and acute inflammation; and (3) the potential toxic effects on nontargeted cells such as lymphocytes. Recent developments of novel inhibitors with differential approaches to modulate NF-κB activity, and the controlled release (local) or bone-targeting drug delivery (systemic) strategies, have largely increased the translational application of NF-κB therapy in bone disorders. Taken together, temporal modulation of NF-κB pathways with the combination of recent advanced bone-targeting drug delivery techniques is a highly translational strategy to reestablish homeostasis in the skeletal system.

  11. SOCS-1/3 participation in FGF-2 signaling to modulate RANK ligand expression in paget's disease of bone.

    PubMed

    Sundaram, Kumaran; Senn, Joseph; Reddy, Sakamuri V

    2013-09-01

    Paget's disease of bone (PDB) is a chronic focal skeletal disorder characterized by excessive bone resorption followed by disorganized new bone formation. Measles virus nucleocapsid (MVNP) is implicated in pathogenesis of PDB. RANK ligand (RANKL), a critical osteoclastogenic factor expressed on bone marrow stromal/preosteoblast cells is upregulated in PDB. We recently demonstrated that fibroblast growth factor-2 (FGF-2) which induces RANKL expression is elevated in PDB. In this study, we hypothesized that FGF-2 modulates suppressors of cytokine signaling (SOCS) to induce RANKL expression in PDB. We identified increased levels of SOCS-1/3 mRNA expression in bone marrow mononuclear cells derived from patients with PDB compared to normal subjects. Interestingly, conditioned media obtained from MVNP transduced osteoclast progenitor cells significantly increased SOCS-1/3 mRNA expression in stromal/preosteoblast cells. We next examined if SOCS participates in FGF-2 signaling to modulate RANKL gene expression. We showed that FGF-2 stimulation significantly increased SOCS-1/3 expression in human bone marrow stromal/preosteoblast cells. In addition, co-expression of SOCS-1/3 with hRANKL gene promoter-luciferase reporter plasmid in marrow stromal cells demonstrated a significant increase in promoter activity without FGF-2 stimulation. Furthermore, siRNA inhibition of STAT-1 suppresses FGF-2 increased SOCS-1/3 expression in these cells. Thus, our results suggest that SOCS participates in FGF-2 modulation of RANKL expression in PDB.

  12. [Results of a combined therapy of patients with metastatic bone diseases].

    PubMed

    Protsenko, V V; Konovalenko, V F; Boĭchuk, S I; Volkov, I B

    2007-01-01

    In the department of bone and soft tissue tumors of Institute of oncology the authors performed a combined treatment (surgery + combined chemotherapy + bisphosphonates + radiation) in 20 patients with bone metastases. Results showed that postoperative complications were observed in 2 patients, new bone lesions in 4 patients. Those satisfactory results prove the efficacy of these treatment options.

  13. Therapeutic impact of low amplitude high frequency whole body vibrations on the osteogenesis imperfecta mouse bone.

    PubMed

    Vanleene, Maximilien; Shefelbine, Sandra J

    2013-04-01

    histological sections, it is possible that WBV reduced bone resorption, resulting in a relative increase in cortical thickness. Whole body vibration appears as a potential effective and innocuous means for increasing bone formation and strength, which is particularly attractive for treating the growing skeleton of children suffering from brittle bone disease or low bone density pathologies without the long term disadvantages of current pharmacological therapies.

  14. Bone marrow mast cell immunophenotyping in adults with mast cell disease: a prospective study of 33 patients.

    PubMed

    Pardanani, A; Kimlinger, T; Reeder, T; Li, C-Y; Tefferi, A

    2004-08-01

    The aberrant co-expression of CD2 and CD25 antigens is the immunophenotypic hallmark of neoplastic mast cells, and has been consistently identified on bone marrow mast cells from patients with indolent mast cell disease (MCD). We prospectively analyzed the bone marrow mast cell immunophenotype by multiparametric flow cytometry (FC) for 33 MCD cases, to examine the role of CD2 and CD25 expression in establishing diagnosis, detecting histologically occult bone marrow mast cell infiltration, and assessing treatment response. While CD25 was almost uniformly expressed, only 6 of 13 patients with indolent MCD, 1 of 8 with aggressive MCD, 2 of 7 with MCD and an associated hematological disorder, and none of the 2 patients with either mast cell leukemia or smoldering systemic mastocytosis, expressed CD2. One of three patients with cutaneous mastocytosis had an aberrant CD2+/CD25+ mast cell population suggesting histologically occult bone marrow involvement. CD25 expression was lost in one patient who achieved complete histologic remission with therapy, but not in two patients who achieved a partial remission. In conclusion, CD25, but not CD2, is a reliable marker for neoplastic mast cells, and CD25 expression indicates histologically occult bone marrow infiltration and residual disease after therapy.

  15. Vanishing bone disease of chest wall and spine with kyphoscoliosis and neurological deficit: A case report and review of literature

    PubMed Central

    Srivastava, Sudhir Kumar; Aggarwal, Rishi Anil; Nemade, Pradip Sharad; Bhoale, Sunil Krishna

    2017-01-01

    Vanishing bone disease is an extremely rare disorder of unknown etiology characterized by idiopathic osteolysis of bone. We describe a case of vanishing bone disease of chest wall and spine with kyphoscoliosis and neurological deficit. A 17-year-old male presented with gradually progressive deformity of back and dorsal compressive myelopathy with nonambulatory power in lower limbs. Radiographs revealed absent 4th–7th ribs on the right side with dorsal kyphoscoliosis and severe canal narrowing at the apex. The patient was given localized radiotherapy and started on a monthly infusion of 4 mg zoledronic acid. Posterior instrumented fusion with anterior reconstruction via posterolateral approach was performed. The patient had a complete neurological recovery at 5 weeks following surgery. At 1 year, anterior nonunion was noted for which transthoracic tricortical bone grafting was done. Bone graft from the patient's mother was used both times. At 7 months following anterior grafting, the alignment was maintained and the patient was asymptomatic; however, fusion at graft-host interface was not achieved. Bisphosphonates and radiotherapy were successful in halting the progress of osteolysis. PMID:28216760

  16. Evolutionary medicine and bone loss in chronic inflammatory diseases – a theory of inflammation-related osteopenia

    PubMed Central

    Straub, Rainer H.; Cutolo, Maurizio; Pacifici, Roberto

    2015-01-01

    Objective Bone loss is typical in chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, ankylosing spondylitis, systemic lupus erythematosus, multiple sclerosis, inflammatory bowel diseases, pemphigus vulgaris, and others. It is also typical in transplantation-related inflammation and during the process of aging. While we recognized that bone loss is tightly linked to immune system activation or inflammaging in the form of acute, chronic active, or chronic smoldering inflammation, bone loss is typically discussed to be an “accident of inflammation”. Methods Extensive literature search in PubMed central. Results Using elements of evolutionary medicine, energy regulation, and neuroendocrine regulation of homeostasis and immune function, we work out that bone waste is an adaptive, evolutionarily positively selected program that is absolutely necessary during acute inflammation. However, when acute inflammation enters a chronic state due to the inability to terminate inflammation (e.g., in autoimmunity or in continuous immunity against microbes), the acute program of bone loss is a misguided adaptive program. Conclusions The article highlights the complexity of interwoven pathways of osteopenia. PMID:26044543

  17. Evidence from Raman Spectroscopy of a Putative Link Between Inherent Bone Matrix Chemistry and Degenerative Joint Disease

    PubMed Central

    Kerns, Jemma G; Gikas, Panagiotis D; Buckley, Kevin; Shepperd, Adam; Birch, Helen L; McCarthy, Ian; Miles, Jonathan; Briggs, Timothy W R; Keen, Richard; Parker, Anthony W; Matousek, Pavel; Goodship, Allen E

    2014-01-01

    Objective Osteoarthritis (OA) is a common debilitating disease that results in degeneration of cartilage and bone in the synovial joints. Subtle changes in the molecular structure of the subchondral bone matrix occur and may be associated with cartilage changes. The aim of this study was to explore whether the abnormal molecular changes observed in the matrix of OA subchondral bone can be identified with Raman spectroscopy. Methods Tibial plateaus from patients undergoing total knee replacement for OA (n = 10) were compared with healthy joints from patients undergoing leg amputation (n = 5; sex- and laterality-matched) and with non-OA cadaveric knee specimens (n = 5; age-matched). The samples were analyzed with Raman spectroscopy, peripheral quantitative computed tomography, and chemical analysis to compare changes in defined load-bearing sites in both the medial and lateral compartments. Results OA subchondral bone matrix changes were detected by Raman spectroscopy. Within each cohort, there was no spectral difference in bone matrix chemistry between the medial and lateral compartments, whereas a significant spectral difference (P < 0.001) was observed between the non-OA and OA specimens. Type I collagen chain ratios were normal in the non-OA specimens but were significantly elevated in the OA specimens. Conclusion In comparing the results of Raman spectroscopy with those obtained by other standard techniques, these findings show, for the first time, that subchondral bone changes, or inherent differences, exist in both the medial and lateral (beneath intact cartilage) compartments of OA knees. The development of Raman spectroscopy as a screening tool, based on molecular-specific modifications in bone, would facilitate the identification of clinical disease, including early molecular changes. PMID:24470432

  18. Osteopenic disease in growing pigs: diagnostic methods using serum and urine calcium and phosphorus values, parathoromone assay, and bone analysis.

    PubMed

    Hagemoser, W A; Goff, J P; Sanderson, T P; Haynes, J S

    2000-11-01

    This research was performed to evaluate the utility of several serum and urine parameters as well as bone ash and plasma parathormone assay to diagnose and monitor diet-related osteopenia in growing pigs. Five diets were tested as follows: calcium-deficient, phosphorus-replete; moderate-deficiency of calcium and phosphorus; marked deficiency of calcium and phosphorus; calcium replete, phosphorus deficient; and vitamin D deficient. Parameters monitored included serum calcium and phosphorus as well as ratios of urine calcium to creatinine, phosphorus to creatinine, calcium to phosphorus, and percent fractional excretions of calcium and phosphorus. Plasma parathormone (PTH) levels were monitored in 2 of 3 experiments. Osteopenic bone differences at necropsy were evaluated by bone density, percent ash, ash per milliliter bone, calcium per milliliter bone, and phosphorus per milliliter bone. Marked change in urine mineral parameters, especially the calcium-to-phosphorus ratio, typically occurred within 1 to 2 days of treatment and preceded significant change in serum mineral or plasma PTH by 2 to 3 weeks. When monitored, plasma PTH levels were elevated following treatment, which confirms the hyperparathyroid state induced by the test diets. Significant differences in bone mineralization between control and treatment diets at necropsy were generally observed. The results of this study indicate that the analysis of urine minerals offers an early, noninvasive technique to investigate diet-associated osteopenic disease in growing pigs, which can be supported further by bone mineral analysis at postmortem using techniques herein described. Several urine mineral reference intervals for application to field investigations are included. Research into application of similar techniques to evaluate calcium and phosphorus homeostasis in pigs of all ages, including gestating and lactating gilts and sows, appears warranted.

  19. VCP Associated Inclusion Body Myopathy and Paget Disease of Bone Knock-In Mouse Model Exhibits Tissue Pathology Typical of Human Disease

    PubMed Central

    Kitazawa, Masashi; Su, Hailing; Tanaja, Jasmin; Dec, Eric; Wallace, Douglas C.; Mukherjee, Jogeshwar; Caiozzo, Vincent; Warman, Matthew; Kimonis, Virginia E.

    2010-01-01

    Dominant mutations in the valosin containing protein (VCP) gene cause inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD). We have generated a knock-in mouse model with the common R155H mutation. Mice demonstrate progressive muscle weakness starting approximately at the age of 6 months. Histology of mutant muscle showed progressive vacuolization of myofibrils and centrally located nuclei, and immunostaining shows progressive cytoplasmic accumulation of TDP-43 and ubiquitin-positive inclusion bodies in quadriceps myofibrils and brain. Increased LC3-II staining of muscle sections representing increased number of autophagosomes suggested impaired autophagy. Increased apoptosis was demonstrated by elevated caspase-3 activity and increased TUNEL-positive nuclei. X-ray microtomography (uCT) images show radiolucency of distal femurs and proximal tibiae in knock-in mice and uCT morphometrics shows decreased trabecular pattern and increased cortical wall thickness. Bone histology and bone marrow derived macrophage cultures in these mice revealed increased osteoclastogenesis observed by TRAP staining suggestive of Paget bone disease. The VCPR155H/+ knock-in mice replicate the muscle, bone and brain pathology of inclusion body myopathy, thus representing a useful model for preclinical studies. PMID:20957154

  20. Chagas disease in bone marrow transplantation: an approach to preemptive therapy.

    PubMed

    Altclas, J; Sinagra, A; Dictar, M; Luna, C; Verón, M T; De Rissio, A M; García, M M; Salgueira, C; Riarte, A

    2005-07-01

    The efficacy of preemptive therapy was evaluated in bone marrow transplantation (BMT) recipients associated with Chagas disease (CD). The criterion to include patients in the protocol was the serological reactivity for CD in recipients and/or donors before transplant. After BMT, the monitoring was performed using the direct Strout method (SM), which detects clinical levels of Trypanosome cruzi parasitemia, and CD conventional serological tests. Monitoring took place during 60 days in ABMT and throughout the immunosuppressive period in allogeneic BMT. Reactivation of CD was diagnosed by detecting T. cruzi parasites in blood or tissues. In primary T. cruzi infection, an additional diagnostic criterion was the serological conversion. A total of 25 CD-BMT patients were included. Two ABMT and four allogeneic BMT recipients showed CD recurrences diagnosed by SM. One patient also showed skin lesions with T. cruzi amastigotes. Benznidazole treatment (Roche Lab), an antiparasitic drug, was prescribed at a dose of 5 mg/kg/day during 4-8 weeks with recovery of patients. Primary T. cruzi infection was not observed. This report proves the relevance of monitoring CD in BMT patients and demonstrates that preemptive therapy was able to abrogate the development of clinical and systemic disease.

  1. The risk of renal disease is increased in lambda myeloma with bone marrow amyloid deposits

    PubMed Central

    Kozlowski, Piotr; Montgomery, Scott; Befekadu, Rahel; Hahn-Strömberg, Victoria

    2017-01-01

    Background Light chain amyloidosis (AL) is a rare deposition disease and is present in 10–15% of patients with myeloma (MM). In contrast to symptomatic AL in MM, presence of bone marrow (BM) amyloid deposits (AD) in MM is not connected to kidney damage. Renal AD but not BM-AD occur mostly in MM with lambda paraprotein (lambda MM). Methods We investigated amyloid presence in BM clots taken at diagnosis in 84 patients with symptomatic MM and compared disease characteristics in MM with kappa paraprotein (kappa MM)/lambda MM with and without BM-AD. Results Lambda MM with BM-AD was compared with kappa MM without BM-AD, kappa MM with BM-AD, and lambda MM without BM-AD: lambda MM with BM-AD patients had a significantly higher mean creatinine level (4.23 mg/dL vs 1.69, 1.14, and 1.28 mg/dL, respectively) and a higher proportion presented with severe kidney failure (6/11 [55%] vs 6/32 [19%], 1/22 [5%], and 3/19 [16%], respectively). Proteinuria was more common in lambda MM with BM-AD patients compared with kappa MM without BM-AD patients (8/11 [73%] vs 5/32 [16%], respectively). Conclusion Kidney damage was more common in lambda MM with BM-AD indicating presence of renal AD. PMID:28293126

  2. Brittle and compaction creep in porous sandstone

    NASA Astrophysics Data System (ADS)

    Heap, Michael; Brantut, Nicolas; Baud, Patrick; Meredith, Philip

    2015-04-01

    Strain localisation in the Earth's crust occurs at all scales, from the fracture of grains at the microscale to crustal-scale faulting. Over the last fifty years, laboratory rock deformation studies have exposed the variety of deformation mechanisms and failure modes of rock. Broadly speaking, rock failure can be described as either dilatant (brittle) or compactive. While dilatant failure in porous sandstones is manifest as shear fracturing, their failure in the compactant regime can be characterised by either distributed cataclastic flow or the formation of localised compaction bands. To better understand the time-dependency of strain localisation (shear fracturing and compaction band growth), we performed triaxial deformation experiments on water-saturated Bleurswiller sandstone (porosity = 24%) under a constant stress (creep) in the dilatant and compactive regimes, with particular focus on time-dependent compaction band formation in the compactive regime. Our experiments show that inelastic strain accumulates at a constant stress in the brittle and compactive regimes leading to the development of shear fractures and compaction bands, respectively. While creep in the dilatant regime is characterised by an increase in porosity and, ultimately, an acceleration in axial strain to shear failure (as observed in previous studies), compaction creep is characterised by a reduction in porosity and a gradual deceleration in axial strain. The overall deceleration in axial strain, AE activity, and porosity change during creep compaction is punctuated by excursions interpreted as the formation of compaction bands. The growth rate of compaction bands formed during creep is lower as the applied differential stress, and hence background creep strain rate, is decreased, although the inelastic strain required for a compaction band remains constant over strain rates spanning several orders of magnitude. We find that, despite the large differences in strain rate and growth rate

  3. Bone Disease in HIV: Recommendations for Screening and Management in the Older Patient.

    PubMed

    Hoy, Jennifer

    2015-07-01

    Availability of potent antiretroviral therapy (ART) has resulted in markedly improved survival for people with human immunodeficiency virus (HIV) infection, as well as an aging HIV population. Increasing morbidity from age-related conditions has resulted in the need to understand the complex roles HIV and its treatment play in the pathogenesis of these conditions. Bone disease and fragility fractures are conditions that occur more frequently in HIV. It is therefore recommended that risk assessment for fragility fracture using the Fracture Risk Assessment Tool (FRAX(®)) algorithm, and low bone mass by dual energy X-ray absorptiometry (DXA) scan, be performed in all patients with HIV infection over the age of 50 years and in those with a history of fragility fracture, and should be repeated every 2-3 years. Because many HIV experts believe that HIV infection and its treatment is a secondary cause of osteoporosis, it should be included as such in the FRAX(®) assessment tool. Management of osteoporosis in HIV infection should follow the same guidelines as that in the general population. Attention to lifestyle factors, including vitamin D replacement, should be emphasized. Whether cessation of tenofovir- or protease inhibitor-based ART regimens should be considered prior to bisphosphonate treatment is currently unknown and should only occur in patients with active alternative ART regimens. The use of bisphosphonates has been shown to be safe and effective in HIV patients, and while there is limited data on second-line osteoporosis regimens, there is no reason to suggest they would not be effective in people with HIV.

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

    PubMed

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

    2016-05-01

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

  5. Osteoporosis in anorexia nervosa: a brittle future?

    PubMed

    Katzman, D K

    2003-02-01

    Anorexia nervosa commonly occurs during adolescence, a critical period for the acquisition of peak bone mass. Osteopenia is an early and serious complication associated with anorexia nervosa. Whether the osteopenia observed in adolescents with anorexia nervosa is reversible is unknown. The possible mechanisms for the osteopenia observed in adolescents with anorexia nervosa are complex and poorly understood. The purpose of this paper is to review a number of the identified factors that influence the attainment of peak bone mass in anorexia nervosa and to examine the best treatment options for optimizing skeletal mineralization in adolescents with anorexia nervosa.

  6. Application of anti-Sclerostin therapy in non-osteoporosis disease models.

    PubMed

    Jacobsen, Christina M

    2017-03-01

    Sclerostin, a known inhibitor of the low density lipoprotein related protein 5 and 6 (LRP5 and LRP6) cell surface signaling receptors, is integral in the maintenance of normal bone mass and strength. Patients with loss of function mutations in SOST or missense mutations in LRP5 that prevent Sclerostin from binding and inhibiting the receptor, have significantly increased bone mass. This observation leads to the development of Sclerostin neutralizing therapies to increase bone mass and strength. Anti-Sclerostin therapy has been shown to be effective at increasing bone density and strength in animal models and patients with osteoporosis. Loss of function of Sost or treatment with a Sclerostin neutralizing antibody improves bone properties in animal models of Osteoporosis Pseudoglioma syndrome (OPPG), likely due to action through the LRP6 receptor, which suggests patients may benefit from these therapies. Sclerostin antibody is effective at improving bone properties in mouse models of Osteogenesis Imperfecta, a genetic disorder of low bone mass and fragility due to type I collagen mutations, in as little as two weeks after initiation of therapy. However, these improvements are due to increases in bone quantity as the quality (brittleness) of bone remains unaffected. Similarly, Sclerostin antibody treatment improves bone density in animal models of other diseases. Sclerostin neutralizing therapies are likely to benefit many patients with genetic disorders of bone, as well as other forms of metabolic bone disease.

  7. Bone image segmentation.

    PubMed

    Liu, Z Q; Liew, H L; Clement, J G; Thomas, C D

    1999-05-01

    Characteristics of microscopic structures in bone cross sections carry essential clues in age determination in forensic science and in the study of age-related bone developments and bone diseases. Analysis of bone cross sections represents a major area of research in bone biology. However, traditional approaches in bone biology have relied primarily on manual processes with very limited number of bone samples. As a consequence, it is difficult to reach reliable and consistent conclusions. In this paper we present an image processing system that uses microstructural and relational knowledge present in the bone cross section for bone image segmentation. This system automates the bone image analysis process and is able to produce reliable results based on quantitative measurements from a large number of bone images. As a result, using large databases of bone images to study the correlation between bone structural features and age-related bone developments becomes feasible.

  8. [CKD-MBD (Chronic Kidney Disease-Mineral and Bone Disorder). Lanthanum carbonate and new phosphate binders in patients with chronic kidney disease].

    PubMed

    Negi, Shigeo; Shigematsu, Takashi

    2010-07-01

    Hyperphosphatemia is a serious complication which has been linked with an increased risk of cardiovascular mortality in patients with chronic kidney disease. Lanthanum carbonate is a novel non-calcium, non-aluminum phosphate-binding agent, and has approved for clinical use in patients on hemodialysis in Japan on March in 2009. Compared to calcium carbonate and sevelamer hydrochloride, lanthanum carbonate is a powerful phosphate binder. There is no evidence of bone toxicity and neurotoxicity of lanthanum carbonate previously reported for aluminium hydroxide. However, further studies are needed to address the longer term toxic effect on bone and other organs.

  9. Theory of friction based on brittle fracture

    USGS Publications Warehouse

    Byerlee, J.D.

    1967-01-01

    A theory of friction is presented that may be more applicable to geologic materials than the classic Bowden and Tabor theory. In the model, surfaces touch at the peaks of asperities and sliding occurs when the asperities fail by brittle fracture. The coefficient of friction, ??, was calculated from the strength of asperities of certain ideal shapes; for cone-shaped asperities, ?? is about 0.1 and for wedge-shaped asperities, ?? is about 0.15. For actual situations which seem close to the ideal model, observed ?? was found to be very close to 0.1, even for materials such as quartz and calcite with widely differing strengths. If surface forces are present, the theory predicts that ?? should decrease with load and that it should be higher in a vacuum than in air. In the presence of a fluid film between sliding surfaces, ?? should depend on the area of the surfaces in contact. Both effects are observed. The character of wear particles produced during sliding and the way in which ?? depends on normal load, roughness, and environment lend further support to the model of friction presented here. ?? 1967 The American Institute of Physics.

  10. Vitamin D, chronic kidney disease and survival: a pluripotent hormone or just another bone drug?

    PubMed

    Biggar, Patrick H; Liangos, Orfeas; Fey, Holger; Brandenburg, Vincent M; Ketteler, Markus

    2011-01-01

    It is now about 40 years ago that the mechanism of renal 1-α-hydroxylation of vitamin D was discovered and characterized. After this seminal observation, the key role of the active vitamin D derivative 1, 25-(OH)2-vitamin D (calcitriol) in calcium homeostasis and bone mineralization, and its specific role in the course of chronic kidney disease (CKD) and renal osteopathy, was unraveled step by step, while the precursor 25-OH-vitamin D (calcidiol) was gradually ignored. Calcitriol and its synthetic analogue alfa-calcidol became the first-line standard drug to tackle secondary hyperparathyroidism (sHPT) in CKD. Potential side-effects, including hypercalcemia, hyperphosphatemia, and vascular calcification, were partly abrogated by developing less calcemic substances such as paricalcitol or maxacalcitol. Thus, TIME Magazine surprised when nominating vitamin D, with regard to its newly discovered pleiotropic actions, as one of the "top medical breakthroughs" in the December issue of 2007. This vote was driven by novel and spectacular insights into the pivotal regulatory role of vitamin D with regard to autoimmune diseases, immune defense, cancer development and progression, and cardiovascular function and disease. More than 30 cell types express the vitamin D receptor (VDR), and more than ten organs in addition to the kidney are capable of paracrine 1-α-hydroxylation. More than 200 genes are under the control of calcitriol. A MEDLINE search performed in December 2009 focusing on the keywords "vitamin D-and-kidney-and-2009" yielded 523 hits. This review intends to give a subjective and CKD-related update on novel biological and clinical insights with relevance to the steroid hormone vitamin D.

  11. ON THE BRITTLENESS OF ENAMEL AND SELECTED DENTAL MATERIALS

    PubMed Central

    Park, S.; Quinn, J. B; Romberg, E.; Arola, D.

    2008-01-01

    Although brittle material behavior is often considered undesirable, a quantitative measure of “brittleness” is currently not used in assessing the clinical merits of dental materials. Objective To quantify and compare the brittleness of human enamel and common dental restorative materials used for crown replacement. Methods Specimens of human enamel were prepared from the 3rd molars of “young” (18≤age≤25) and “old” (50≤age) patients. The hardness, elastic modulus and apparent fracture toughness were characterized as a function of distance from the DEJ using indentation approaches. These properties were then used in estimating the brittleness according to a model that accounts for the competing dissipative processes of deformation and fracture. The brittleness of selected porcelain, ceramic and Micaceous Glass Ceramic (MGC) dental materials was estimated and compared with that of the enamel. Results The average brittleness of the young and old enamel increased with distance from the DEJ. For the old enamel the average brittleness increased from approximately 300 µm−1 at the DEJ to nearly 900 µm−1 at the occlusal surface. While there was no significant difference between the two age groups at the DEJ, the brittleness of the old enamel was significantly greater (and up to 4 times higher) than that of the young enamel near the occlusal surface. The brittleness numbers for the restorative materials were up to 90% lower than that of young occlusal enamel. Significance The brittleness index could serve as a useful scale in the design of materials used for crown replacement, as well as a quantitative tool for characterizing degradation in the mechanical behavior of enamel. PMID:18436299

  12. Targeting cells of the myeloid lineage attenuates pain and disease progression in a prostate model of bone cancer.

    PubMed

    Thompson, Michelle L; Jimenez-Andrade, Juan M; Chartier, Stephane; Tsai, James; Burton, Elizabeth A; Habets, Gaston; Lin, Paul S; West, Brian L; Mantyh, Patrick W

    2015-09-01

    Tumor cells frequently metastasize to bone where they can generate cancer-induced bone pain (CIBP) that can be difficult to fully control using available therapies. Here, we explored whether PLX3397, a high-affinity small molecular antagonist that binds to and inhibits phosphorylation of colony-stimulating factor-1 receptor, the tyrosine-protein kinase c-Kit, and the FMS-like tyrosine kinase 3, can reduce CIBP. These 3 targets all regulate the proliferation and function of a subset of the myeloid cells including macrophages, osteoclasts, and mast cells. Preliminary experiments show that PLX3397 attenuated inflammatory pain after formalin injection into the hind paw of the rat. As there is an inflammatory component in CIBP, involving macrophages and osteoclasts, the effect of PLX3397 was explored in a prostate model of CIBP where skeletal pain, cancer cell proliferation, tumor metastasis, and bone remodeling could be monitored in the same animal. Administration of PLX3397 was initiated on day 14 after prostate cancer cell injection when the tumor was well established, and tumor-induced bone remodeling was first evident. Over the next 6 weeks, sustained administration of PLX3397 attenuated CIBP behaviors by approximately 50% and was equally efficacious in reducing tumor cell growth, formation of new tumor colonies in bone, and pathological tumor-induced bone remodeling. Developing a better understanding of potential effects that analgesic therapies have on the tumor itself may allow the development of therapies that not only better control the pain but also positively impact disease progression and overall survival in patients with bone cancer.

  13. A promising approach for treatment of tumor-induced bone diseases: utilizing bisphosphonate derivatives of nucleoside antimetabolites.

    PubMed

    Reinholz, Monica M; Zinnen, Shawn P; Dueck, Amylou C; Dingli, David; Reinholz, Gregory G; Jonart, Leslie A; Kitzmann, Kathleen A; Bruzek, Amy K; Negron, Vivian; Abdalla, Abdalla K; Arendt, Bonnie K; Croatt, Anthony J; Sanchez-Perez, Luis; Sebesta, David P; Lönnberg, Harri; Yoneda, Toshiyuki; Nath, Karl A; Jelinek, Diane F; Russell, Stephen J; Ingle, James N; Spelsberg, Thomas C; Dixon, Henry B F Hal; Karpeisky, Alexander; Lingle, Wilma L

    2010-07-01

    Despite palliative treatments, tumor-induced bone disease (TIBD) remains highly debilitating for many cancer patients and progression typically results in death within two years. Therefore, more effective therapies with enhanced anti-resorptive and cytotoxic characteristics are needed. We developed bisphosphonate-chemotherapeutic conjugates designed to bind bone and hydrolyze, releasing both compounds, thereby targeting both osteoclasts and tumor cells. This study examined the effects of our lead compound, MBC-11 (the anhydride formed between arabinocytidine (AraC)-5'-phosphate and etidronate), on bone tumor burden, bone volume, femur bone mineral density (BMD), and overall survival using two distinct mouse models of TIBD, the 4T1/luc breast cancer and the KAS-6/1-MIP1alpha multiple myeloma models. In mice orthotopically inoculated with 4T1/luc mouse mammary cells, MBC-11 (0.04 microg/day; s.c.) reduced the incidence of bone metastases to 40% (4/10), compared to 90% (9/10; p=0.057) and 100% (5/5; p=0.04) of PBS- or similarly-dosed, zoledronate-treated mice, respectively. MBC-11 also significantly decreased bone tumor burden compared to PBS- or zoledronate-treated mice (p=0.021, p=0.017, respectively). MBC-11 and zoledronate (0.04 microg/day) significantly increased bone volume by two- and four-fold, respectively, compared to PBS-treated mice (p=0.005, p<0.001, respectively). In mice systemically injected with human multiple myeloma KAS-6/1-MIP1alpha cells, 0.04 and 4.0 microg/day MBC-11 improved femur BMD by 13% and 16%, respectively, compared to PBS (p=0.025, p=0.017, respectively) at 10 weeks post-tumor cell injection and increased mean survival to 95 days compared to 77 days in mice treated with PBS (p=0.047). Similar doses of zoledronate also improved femur BMD (p< or =0.01 vs PBS) and increased mean survival to 86 days, but this was not significantly different than in PBS-treated mice (p=0.53). These results demonstrate that MBC-11 decreases bone tumor burden

  14. Age-dependence of power spectral density and fractal dimension of bone mineralized matrix in atomic force microscope topography images: potential correlates of bone tissue age and bone fragility in female femoral neck trabeculae

    PubMed Central

    Milovanovic, Petar; Djuric, Marija; Rakocevic, Zlatko

    2012-01-01

    There is an increasing interest in bone nano-structure, the ultimate goal being to reveal the basis of age-related bone fragility. In this study, power spectral density (PSD) data and fractal dimensions of the mineralized bone matrix were extracted from atomic force microscope topography images of the femoral neck trabeculae. The aim was to evaluate age-dependent differences in the mineralized matrix of human bone and to consider whether these advanced nano-descriptors might be linked to decreased bone remodeling observed by some authors and age-related decline in bone mechanical competence. The investigated bone specimens belonged to a group of young adult women (n = 5, age: 20–40 years) and a group of elderly women (n = 5, age: 70–95 years) without bone diseases. PSD graphs showed the roughness density distribution in relation to spatial frequency. In all cases, there was a fairly linear decrease in magnitude of the power spectra with increasing spatial frequencies. The PSD slope was steeper in elderly individuals (−2.374 vs. −2.066), suggesting the dominance of larger surface morphological features. Fractal dimension of the mineralized bone matrix showed a significant negative trend with advanced age, declining from 2.467 in young individuals to 2.313 in the elderly (r = 0.65, P = 0.04). Higher fractal dimension in young women reflects domination of smaller mineral grains, which is compatible with the more freshly remodeled structure. In contrast, the surface patterns in elderly individuals were indicative of older tissue age. Lower roughness and reduced structural complexity (decreased fractal dimension) of the interfibrillar bone matrix in the elderly suggest a decline in bone toughness, which explains why aged bone is more brittle and prone to fractures. PMID:22946475

  15. Paget Disease of Bone: Mapping of Two Loci at 5q35-qter and 5q31

    PubMed Central

    Laurin, Nancy; Brown, Jacques P.; Lemainque, Arnaud; Duchesne, Annie; Huot, Denys; Lacourcière, Yves; Drapeau, Gervais; Verreault, Jean; Raymond, Vincent; Morissette, Jean

    2001-01-01

    Paget disease of bone is characterized by focal increases of the bone-remodeling process. It is the second most common metabolic bone disease after osteoporosis. Genetic factors play a major role in the etiology of Paget disease of bone, and two loci have been mapped for the disorder: PDB1 and PDB2. The gene(s) causing the typical form of the disorder remains to be characterized. To decipher the molecular basis of Paget disease of bone, we performed genetic linkage analysis in 24 large French Canadian families (479 individuals) in which the disorder was segregating as an autosomal dominant trait. After exclusion of PDB2, a genomewide scan was performed on the three most informative family nuclei. LOD scores >1.0 were observed at seven locations. The 24 families were then used to detect strong evidence for linkage to chromosome 5q35-qter. Under heterogeneity, a maximum LOD score of 8.58 was obtained at D5S2073, at θ=.1. The same characteristic haplotype was carried by all patients in eight families, suggesting a founder effect. A recombination event in a key family confined the disease region within a 6-cM interval between D5S469 and the telomere. The 16 other families, with very low conditional probability of linkage to 5q35-qter, were further used, to map a second locus at 5q31. Under heterogeneity, a maximum LOD score of 3.70 was detected at D5S500 with θ=.00. Recombination events refined the 5q31 region within 12.2 cM, between D5S642 and D5S1972. These observations demonstrate the mapping of two novel loci for Paget disease of bone and provide further evidence for genetic heterogeneity of this highly prevalent disorder. It is proposed that the 5q35-qter and 5q31 loci be named “PDB3” and “PDB4,” respectively. PMID:11473345

  16. Transcriptomic profile induced in bone marrow mesenchymal stromal cells after interaction with multiple myeloma cells: implications in myeloma progression and myeloma bone disease.

    PubMed

    Garcia-Gomez, Antonio; De Las Rivas, Javier; Ocio, Enrique M; Díaz-Rodríguez, Elena; Montero, Juan C; Martín, Montserrat; Blanco, Juan F; Sanchez-Guijo, Fermín M; Pandiella, Atanasio; San Miguel, Jesús F; Garayoa, Mercedes

    2014-09-30

    Despite evidence about the implication of the bone marrow (BM) stromal microenvironment in multiple myeloma (MM) cell growth and survival, little is known about the effects of myelomatous cells on BM stromal cells. Mesenchymal stromal cells (MSCs) from healthy donors (dMSCs) or myeloma patients (pMSCs) were co-cultured with the myeloma cell line MM.1S, and the transcriptomic profile of MSCs induced by this interaction was analyzed. Deregulated genes after co-culture common to both d/pMSCs revealed functional involvement in tumor microenvironment cross-talk, myeloma growth induction and drug resistance, angiogenesis and signals for osteoclast activation and osteoblast inhibition. Additional genes induced by co-culture were exclusively deregulated in pMSCs and predominantly associated to RNA processing, the ubiquitine-proteasome pathway, cell cycle regulation, cellular stress and non-canonical Wnt signaling. The upregulated expression of five genes after co-culture (CXCL1, CXCL5 and CXCL6 in d/pMSCs, and Neuregulin 3 and Norrie disease protein exclusively in pMSCs) was confirmed, and functional in vitro assays revealed putative roles in MM pathophysiology. The transcriptomic profile of pMSCs co-cultured with myeloma cells may better reflect that of MSCs in the BM of myeloma patients, and provides new molecular insights to the contribution of these cells to MM pathophysiology and to myeloma bone disease.

  17. Transcriptomic profile induced in bone marrow mesenchymal stromal cells after interaction with multiple myeloma cells: implications in myeloma progression and myeloma bone disease

    PubMed Central

    Garcia-Gomez, Antonio; Las Rivas, Javier De; Ocio, Enrique M.; Díaz-Rodríguez, Elena; Montero, Juan C.; Martín, Montserrat; Blanco, Juan F.; Sanchez-Guijo, Fermín M.; Pandiella, Atanasio; San Miguel, Jesús F.; Garayoa, Mercedes

    2014-01-01

    Despite evidence about the implication of the bone marrow (BM) stromal microenvironment in multiple myeloma (MM) cell growth and survival, little is known about the effects of myelomatous cells on BM stromal cells. Mesenchymal stromal cells (MSCs) from healthy donors (dMSCs) or myeloma patients (pMSCs) were co-cultured with the myeloma cell line MM.1S, and the transcriptomic profile of MSCs induced by this interaction was analyzed. Deregulated genes after co-culture common to both d/pMSCs revealed functional involvement in tumor microenvironment cross-talk, myeloma growth induction and drug resistance, angiogenesis and signals for osteoclast activation and osteoblast inhibition. Additional genes induced by co-culture were exclusively deregulated in pMSCs and predominantly associated to RNA processing, the ubiquitine-proteasome pathway, cell cycle regulation, cellular stress and non-canonical Wnt signaling. The upregulated expression of five genes after co-culture (CXCL1, CXCL5 and CXCL6 in d/pMSCs, and Neuregulin 3 and Norrie disease protein exclusively in pMSCs) was confirmed, and functional in vitro assays revealed putative roles in MM pathophysiology. The transcriptomic profile of pMSCs co-cultured with myeloma cells may better reflect that of MSCs in the BM of myeloma patients, and provides new molecular insights to the contribution of these cells to MM pathophysiology and to myeloma bone disease. PMID:25268740

  18. [Features of bone and muscular diseases in accordance with physical exertion level in workers].

    PubMed

    Vlasova, E M; Alekseev, V B

    2012-01-01

    The authors studied changes in development and structure of bone and muscular disorders in industrial workers of Perm area. The workers' examination considered features of physical overload during the working process. The authors revealed developmental peculiarities of bone and muscular system in various occupational groups of metallurgists, oil extractors, machinery building workers. The article shows necessity of interdisciplinary approach and observation of the workers to prevent progression of bone and muscular disorders.

  19. Partial resolution of bone lesions. A child with severe combined immunodeficiency disease and adenosine deaminase deficiency after enzyme-replacement therapy

    SciTech Connect

    Yulish, B.S.; Stern, R.C.; Polmar, S.H.

    1980-01-01

    A child with severe combined immunodeficiency disease and adenosine deaminase deficiency, with characteristic bone dysplasia, was treated with transfusions of frozen irradiated RBCs as a means of enzyme replacement. This therapy resulted in restoration of immunologic competence and partial resolution of the bone lesions. Although the natural history of these lesions without therapy is not known, enzyme-replacement therapy may have played a role in the resolution of this patient's bone lesions.

  20. CYR61/CCN1 overexpression in the myeloma microenvironment is associated with superior survival and reduced bone disease.

    PubMed

    Johnson, Sarah K; Stewart, James P; Bam, Rakesh; Qu, Pingping; Barlogie, Bart; van Rhee, Frits; Shaughnessy, John D; Epstein, Joshua; Yaccoby, Shmuel

    2014-09-25

    Secreted protein CCN1, encoded by CYR61, is involved in wound healing, angiogenesis, and osteoblast differentiation. We identified CCN1 as a microenvironmental factor produced by mesenchymal cells and overexpressed in bones of a subset of patients with monoclonal gammopathy of undetermined significance (MGUS), asymptomatic myeloma (AMM), and multiple myeloma (MM). Our analysis showed that overexpression of CYR61 was independently associated with superior overall survival of MM patients enrolled in our Total Therapy 3 protocol. Moreover, elevated CCN1 was associated with a longer time for MGUS/AMM to progress to overt MM. During remission from MM, high levels of CCN1 were associated with superior progression-free and overall survival and stratified patients with molecularly defined high-risk MM. Recombinant CCN1 directly inhibited in vitro growth of MM cells, and overexpression of CYR61 in MM cells reduced tumor growth and prevented bone destruction in vivo in severe combined immunodeficiency-hu mice. Signaling through αvβ3 was required for CCN1 prevention of bone disease. CYR61 expression may signify early perturbation of the microenvironment before conversion to overt MM and may be a compensatory mechanism to control MM progression. Therapeutics that upregulate CYR61 should be investigated for treating MM bone disease.

  1. Topical HPMC/S-Nitrosoglutathione Solution Decreases Inflammation and Bone Resorption in Experimental Periodontal Disease in Rats

    PubMed Central

    Martins, Conceição S.; Leitão, Renata F. C.; Costa, Deiziane V. S.; Melo, Iracema M.; Santos, Glaylton S.; Lima, Vilma; Baldim, Victor; Wong, Deysi V. T.; Bonfim, Luana E.; Melo, Cíntia B.; Brito, Gerly A. C.

    2016-01-01

    S-nitrosoglutathione (GSNO) is a nitric oxide (NO) donor, which exerts antioxidant, anti-inflammatory, and microbicidal actions. Intragingival application of GSNO was already shown to decrease alveolar bone loss, inflammation and oxidative stress in an experimental periodontal disease (EPD) model. In the present study, we evaluated the potential therapeutic effect of topical applications of hydroxypropylmethylcellulose (HPMC)/GSNO solutions on EPD in Wistar rats. EPD was induced by placing a sterilized nylon (3.0) thread ligature around the cervix of the second left upper molar of the animals, which received topical applications of a HPMC solutions containing GSNO 2 or 10 mM or vehicle (HPMC solution), 1 h prior to the placement of the ligature and then twice daily until sacrifice on day 11. Treatment with HPMC/GSNO 10 mM solution significantly reduced alveolar bone loss, oxidative stress and TNF-α e IL-1β levels in the surrounding gingival tissue, and led to a decreased transcription of RANK and TNF-α genes and elevated bone alkaline phosphatase, compared to the HPMC group. In conclusion, topical application of HPMC/GSNO solution is a potential treatment to reduce inflammation and bone loss in periodontal disease. PMID:27116554

  2. Context Matters: Distinct Disease Outcomes as a Result of Crebbp Hemizygosity in Different Mouse Bone Marrow Compartments

    PubMed Central

    Zhou, Ting; Perez, Stephanie N.; Cheng, Ziming; Kinney, Marsha C.; Lemieux, Madeleine E.; Scott, Linda M.; Rebel, Vivienne I.

    2016-01-01

    Perturbations in CREB binding protein (CREBBP) are associated with hematopoietic malignancies, including myelodysplastic syndrome (MDS). Mice hemizygous for Crebbp develop myelodysplasia with proliferative features, reminiscent of human MDS/myeloproliferative neoplasm-unclassifiable (MDS/MPN-U), and a proportion goes on to develop acute myeloid leukemia (AML). We have also shown that the Crebbp+/- non-hematopoietic bone marrow microenvironment induces excessive myeloproliferation of wild-type cells. We now report that transplantation of unfractionated Crebbp+/- bone marrow into wild-type recipients resulted in either early-onset AML or late-onset MDS and MDS/MPN-U. In contrast, purified Lin-Sca-1+c-Kit++ cells primarily gave rise to MDS with occasional transformation to AML. Furthermore, Crebbp+/- common myeloid progenitors and granulocyte/macrophage progenitors could trigger skewed myelopoiesis, myelodysplasia and late-onset AML. Surprisingly, the phenotypically abnormal cells were all of wild-type origin. MDS, MPN and AML can thus all be transferred from Crebbp+/- BM to wild-type hosts but fractionated bone marrow does not recapitulate the full disease spectrum of whole bone marrow, indicating that not only mutational status but also cellular context contribute to disease outcome. This has important consequences for structuring and interpreting future investigations into the underlying mechanisms of myeloid malignancies as well as for their treatment. PMID:27427906

  3. CYR61/CCN1 overexpression in the myeloma microenvironment is associated with superior survival and reduced bone disease

    PubMed Central

    Stewart, James P.; Bam, Rakesh; Qu, Pingping; Barlogie, Bart; van Rhee, Frits; Shaughnessy, John D.; Epstein, Joshua; Yaccoby, Shmuel

    2014-01-01

    Secreted protein CCN1, encoded by CYR61, is involved in wound healing, angiogenesis, and osteoblast differentiation. We identified CCN1 as a microenvironmental factor produced by mesenchymal cells and overexpressed in bones of a subset of patients with monoclonal gammopathy of undetermined significance (MGUS), asymptomatic myeloma (AMM), and multiple myeloma (MM). Our analysis showed that overexpression of CYR61 was independently associated with superior overall survival of MM patients enrolled in our Total Therapy 3 protocol. Moreover, elevated CCN1 was associated with a longer time for MGUS/AMM to progress to overt MM. During remission from MM, high levels of CCN1 were associated with superior progression-free and overall survival and stratified patients with molecularly defined high-risk MM. Recombinant CCN1 directly inhibited in vitro growth of MM cells, and overexpression of CYR61 in MM cells reduced tumor growth and prevented bone destruction in vivo in severe combined immunodeficiency-hu mice. Signaling through αvβ3 was required for CCN1 prevention of bone disease. CYR61 expression may signify early perturbation of the microenvironment before conversion to overt MM and may be a compensatory mechanism to control MM progression. Therapeutics that upregulate CYR61 should be investigated for treating MM bone disease. PMID:25061178

  4. Graft-versus-Host Disease-Associated Vulvovaginal Symptoms after Bone Marrow Transplantation.

    PubMed

    Chung, Christopher P; Sargent, Rachel E; Chung, Nadia T; Lacey, James V; Wakabayashi, Mark T

    2016-02-01

    We conducted a retrospective review to assess the prevalence of graft-versus-host disease (GVHD)-associated gynecologic conditions among bone marrow transplantation (BMT) patients at City of Hope Medical Center. We calculated the associations among the estimated risks of various gynecologic complications, including vaginal stenosis, by performing chi-square tests and t-test statistics. Between 2010 and 2014, 180 patients were referred to the gynecologic clinic after their BMT. One hundred twenty-four patients (69%) had GVHD; among these patients, 51 (41%) experienced dyspareunia and 43 (35%) had vaginal stenosis. GVHD patients were significantly more likely to have vaginal stenosis (P < .0001), more likely to have used a vaginal dilator (P = .0008), and less likely to have urinary incontinence (UI) than those without GVHD (P < .001). There was no difference in developing pelvic organ prolapse (POP) in patients with or without GVHD (P = .4373). GVHD was a common complication after allogenic BMT. Patients with BMT were more likely to have vulvovaginal symptoms, such as dyspareunia and pelvic pain. Patients with GVHD are at high risk for vaginal stenosis requiring the use of a vaginal dilator. However, they are at low risk for developing UI and POP.

  5. Bone age and factors affecting skeletal maturation at diagnosis of paediatric Cushing's disease.

    PubMed

    Acharya, Shrikrishna V; Gopal, Raju A; Lila, Anurag; Menon, Padma S; Bandgar, Tushar R; Shah, Nalini S

    2010-12-01

    Paediatric Cushing's disease (CD) is usually associated with growth retardation, but there are only few published data on skeletal maturation at diagnosis. We analysed factors contributing to skeletal maturation and final height in Asian Indian patients with paediatric CD. We conducted retrospective analysis of 48 patients (29 males; 19 females) with mean age: 14.84 years at diagnosis (range 9-19 years). A single observer using the Greulich Pyle method determined the bone age (BA) of each child. BA delay, i.e. the difference between chronological age (CA) and BA, was compared with clinical and biochemical variables. BA delay was present in 35/48 (73%) patients (mean delay 1.6 years, range 0.5-5 years) and correlated negatively with height SDS (r = -0.594, P < 0.001) and positively with CA at diagnosis (r = 0.247, P < 0.05). There was no correlation with duration of symptoms before diagnosis, basal cortisol, midnight cortisol, ACTH or percentage suppression of low dose dexamethasone suppression cortisol (LDDST). We could not demonstrate any relationship between the duration of history before diagnosis and height SDS at final height. Mean final height SDS in patients was -1.84. We found that most children with CD had delayed BA and correlated significantly with CA and height SDS at diagnosis. Early diagnosis may reduce delay in skeletal maturation and thus contribute to optimal catch-up growth.

  6. Does taurine deficiency cause metabolic bone disease and rickets in polar bear cubs raised in captivity?

    PubMed

    Chesney, Russell W; Hedberg, Gail E; Rogers, Quinton R; Dierenfeld, Ellen S; Hollis, Bruce E; Derocher, Andrew; Andersen, Magnus

    2009-01-01

    Rickets and fractures have been reported in captive polar bears. Taurine (TAU) is key for the conjugation of ursodeoxycholic acid (UDCA), a bile acid unique to bears. Since TAU-conjugated UDCA optimizes fat and fat-soluble vitamin absorption, we asked if TAU deficiency could cause vitamin D malabsorption and lead to metabolic bone disease in captive polar bears. We measured TAU levels in plasma (P) and whole blood (WB) from captive and free-ranging cubs and adults, and vitamin D3 and TAU concentrations in milk samples from lactating sows. Plasma and WB TAU levels were significantly higher in cubs vs captive and free-ranging adult bears. Vitamin D in polar bear milk was 649.2 +/- 569.2 IU/L, similar to that found in formula. The amount of TAU in polar bear milk is 3166.4 +/- 771 nmol/ml, 26-fold higher than in formula. Levels of vitamin D in bear milk and formula as well as in plasma do not indicate classical nutritional vitamin D deficiency. Higher dietary intake of TAU by free-ranging cubs may influence bile acid conjugation and improve vitamin D absorption.

  7. Dietary phosphorus excess: a risk factor in chronic bone, kidney, and cardiovascular disease?

    PubMed

    Uribarri, Jaime; Calvo, Mona S

    2013-09-01

    There is growing evidence in the nephrology literature supporting the deleterious health effect of excess dietary phosphorus intake. This issue has largely escaped the attention of nutrition experts until this symposium, which raised the question of whether the same health concerns should be extended to the general population. The potential hazard of a high phosphorus intake in the healthy population is illustrated by findings from acute and epidemiologic studies. Acute studies in healthy young adults demonstrate that phosphorus intakes in excess of nutrient needs may significantly disrupt the hormonal regulation of phosphorus contributing to disordered mineral metabolism, vascular calcification, bone loss, and impaired kidney function. One of the hormonal factors acutely affected by dietary phosphorus loading is fibroblast growth factor-23, which may be a key factor responsible for many of the cardiovascular disease (CVD) complications of high phosphorus intake. Increasingly, large epidemiological studies suggest that mild elevations of serum phosphorus within the normal range are associated with CVD risk in healthy populations. Few population studies link high dietary phosphorus intake to mild changes in serum phosphorus due to study design issues specific to phosphorus and inaccurate nutrient composition databases. The increasing phosphorus intake due to the use of phosphorus-containing ingredients in processed food and the growing consumption of processed convenience and fast foods is an important factor that needs to be emphasized.

  8. [Disorders of carbohydrate metabolism, dyslipidemia, and bone metabolic disease after hematopoietic stem cell transplantation].

    PubMed

    Wędrychowicz, Anna; Starzykk, Jerzy

    2013-01-01

    Among long-term survivors after hematopoietic stem cell transplantation (HSCT) late endocrine complications are observed in 20-50%. Very often these complications influence significantly the patient´s life and have to be treated till the end of life. Their proper prevention and monitoring are extremely important in patients who underwent HSCT during childhood. Since the 90s of the last millennium/century, thyroid dysfunction, disorders of somatic and sexual development, and disturbances of fertility have been presented in several publications. In the paper, less known endocrine complications after HSCT published in the last years are discussed. Disorders of carbohydrate metabolism, post-transplant diabetes and insulin resistance are presented. Moreover, dyslipidemia, hypertension, and post-transplant bone metabolic disease are demonstrated/shown. The paper describes the etiopathogenesis, methods of prevention as well as treatment and the results of the treatment of these endocrine complications after HSCT. Moreover, actual recommendations for screening and prevention of endocrine complications in long-term HCT survivors are presented.

  9. Gorham-Stout Disease: a Clinical Case Report and Immunological Mechanisms in Bone Erosion.

    PubMed

    Franco-Barrera, Maria José; Zavala-Cerna, Maria Guadalupe; Aguilar-Portillo, Georgina; Sánchez-Gomez, Diana Brisa; Torres-Bugarin, Olivia; Franco-Barrera, Miguel Angel; Roa-Encarnacion, Carlos Manuel

    2017-02-01

    Gorham-Stout disease (GSD) is a rare condition of osteolysis with excessive lymphangiogenesis within bone tissue. The etiology of this condition remains unknown but seems to affect mainly children and young adults of both genders all over the world. Unfortunately, there is no standardized method for diagnosis; however, histopathology remains as the gold standard. This condition is often misdiagnosed due to its varying clinical presentations from case-to-case. Here, we report the case of an 8-year-old girl who presented with chronic mandibular pain during mastication and received multiple antibiotic treatment due to infectious origin suspicion. After integrating information from clinical manifestations, radiographic, laboratory, and histopathology information, she was diagnosed with GSD. Additionally, due to the lack of literature with respect to insights into biological mechanisms and standardized treatment for this condition, we underwent a literature revision to provide information related to activation of cells from the immune system, such as macrophages, T-cells, and dendritic cells, and their contribution to the lymphangiogenesis, angiogenesis, and osteoclastogenic process in GSD. It is important to consider these mechanisms in patients with GSD, especially since new studies performed in earlier stages are required to confirm their use as novel diagnostic tools and find new possibilities for treatment.

  10. Benchmarking analogue models of brittle thrust wedges

    NASA Astrophysics Data System (ADS)

    Schreurs, Guido; Buiter, Susanne J. H.; Boutelier, Jennifer; Burberry, Caroline; Callot, Jean-Paul; Cavozzi, Cristian; Cerca, Mariano; Chen, Jian-Hong; Cristallini, Ernesto; Cruden, Alexander R.; Cruz, Leonardo; Daniel, Jean-Marc; Da Poian, Gabriela; Garcia, Victor H.; Gomes, Caroline J. S.; Grall, Céline; Guillot, Yannick; Guzmán, Cecilia; Hidayah, Triyani Nur; Hilley, George; Klinkmüller, Matthias; Koyi, Hemin A.; Lu, Chia-Yu; Maillot, Bertrand; Meriaux, Catherine; Nilfouroushan, Faramarz; Pan, Chang-Chih; Pillot, Daniel; Portillo, Rodrigo; Rosenau, Matthias; Schellart, Wouter P.; Schlische, Roy W.; Take, Andy; Vendeville, Bruno; Vergnaud, Marine; Vettori, Matteo; Wang, Shih-Hsien; Withjack, Martha O.; Yagupsky, Daniel; Yamada, Yasuhiro

    2016-11-01

    We performed a quantitative comparison of brittle thrust wedge experiments to evaluate the variability among analogue models and to appraise the reproducibility and limits of model interpretation. Fifteen analogue modeling laboratories participated in this benchmark initiative. Each laboratory received a shipment of the same type of quartz and corundum sand and all laboratories adhered to a stringent model building protocol and used the same type of foil to cover base and sidewalls of the sandbox. Sieve structure, sifting height, filling rate, and details on off-scraping of excess sand followed prescribed procedures. Our analogue benchmark shows that even for simple plane-strain experiments with prescribed stringent model construction techniques, quantitative model results show variability, most notably for surface slope, thrust spacing and number of forward and backthrusts. One of the sources of the variability in model results is related to slight variations in how sand is deposited in the sandbox. Small changes in sifting height, sifting rate, and scraping will result in slightly heterogeneous material bulk densities, which will affect the mechanical properties of the sand, and will result in lateral and vertical differences in peak and boundary friction angles, as well as cohesion values once the model is constructed. Initial variations in basal friction are inferred to play the most important role in causing model variability. Our comparison shows that the human factor plays a decisive role, and even when one modeler repeats the same experiment, quantitative model results still show variability. Our observations highlight the limits of up-scaling quantitative analogue model results to nature or for making comparisons with numerical models. The frictional behavior of sand is highly sensitive to small variations in material state or experimental set-up, and hence, it will remain difficult to scale quantitative results such as number of thrusts, thrust spacing

  11. Periodontal disease-associated compensatory expression of osteoprotegerin is lost in type 1 diabetes mellitus and correlates with alveolar bone destruction by regulating osteoclastogenesis.

    PubMed

    Silva, Juliete Aparecida F; Lopes Ferrucci, Danilo; Peroni, Luis Antônio; de Paula Ishi, Eduardo; Rossa-Junior, Carlos; Carvalho, Hernandes F; Stach-Machado, Dagmar Ruth

    2012-01-01

    Alveolar bone resorption results from the inflammatory response to periodontal pathogens. Systemic diseases that affect the host response, such as type 1 diabetes mellitus (DM1), can potentiate the severity of periodontal disease (PD) and accelerate bone resorption. However, the biological mechanisms by which DM1 modulates PD are not fully understood. The aim of this study was to determine the influence of DM1 on alveolar bone resorption and to evaluate the role of receptor activator of nuclear factor-kappaB ligand (RANKL)/osteoprotegerin (OPG) in osteoclastogenesis in rats. PD was induced by means of ligature in nondiabetic and in streptozotocyn-induced DM1 rats. Morphological and morphometric analyses, stereology and osteoclast counting were performed. RANKL and OPG mRNA levels, protein content, and location were determined. PD caused alveolar bone resorption, increased the number of osteoclasts in the alveolar bone crest and also promoted changes in RANKL/OPG mRNA expression. DM1 alone showed alveolar bone destruction and an increased number of osteoclasts at the periapical and furcal regions. DM1 exacerbated these characteristics, with a greater impact on bone structure, resulting in a low OPG content and a higher RANKL/OPG ratio, which correlated with prominent osteoclastogenesis. This work demonstrates that the effects