acid-phosphatase and Osteitis-Deformans

We targeted the MVNP gene to the OCL lineage in transgenic mice. These mice developed abnormal OCLs and bone lesions similar to those found in Paget's patients. These results show that persistent expression of MVNP in OCLs can induce pagetic-like bone lesions in vivo.. Paget's disease (PD) is one of the most exaggerated examples of abnormal bone remodeling, with increased bone resorption and excessive new bone formation. However, its etiology is unclear. A viral etiology for PD has been suggested based on the presence of paramyxoviral-like nuclear inclusions, detection of measles virus nucleocapsid (MVNP) mRNA or protein in osteoclasts (OCLs) from PD lesions, and in vitro studies showing that transfection of normal OCL precursors with the MVNP gene results in formation of OCLs that express a pagetic phenotype (increased numbers of OCLs; increased responsivity to 1,25(OH)(2)D(3), RANKL, and TNF-alpha; increased expression of the TAF(II)-17 gene, and increased bone resorption capacity).. We targeted MVNP to cells in the OCL lineage in transgenic mice using the TRACP promoter.. Histomorphometric analysis showed that there was a 64% increase in OCL perimeter (p = 6.0002) and 37% increase in osteoblast (OBL) perimeter in MVNP mice. In a mouse that was 14 months of age, there was a 225% increase in OBL perimeter and 149% in OBL perimeter. This was accompanied by increased cancellous bone volume (83%) and trabecular width (47%) and number (25%), with a marked increase in the amount of woven bone. In contrast, cancellous bone volume decreased between 3 and 12 months in wildtype (WT) mice, whereas cancellous bone volume in MVNP mice increased over the same time period. Ex vivo studies showed that the numbers of OCLs formed in marrow cultures from MVNP mice were increased, and the OCLs were hyper-responsive to 1,25(OH)(2)D(3) and had an increased bone resorbing capacity compared with WT cultures.. These results show that expression of MVNP in OCL in vivo results in a bone phenotype that is characteristic of PD.

Topics: Acid Phosphatase; Animals; Calcitriol; Cells, Cultured; Disease Models, Animal; Humans; Isoenzymes; Mice; Mice, Transgenic; Osteitis Deformans; Osteoclasts; Promoter Regions, Genetic; Tartrate-Resistant Acid Phosphatase

Rapid detection of the exact changes in bone remodelling is exceptionally important. In this paper, the latest bone remodelling biochemical markers are reviewed. Some of them have already been used for a long time, and their utility has been widely demonstrated. The newest ones, in experimental stage, can be used as a complement to the others. The bone remodelling markers reviewed are: 1) Alkaline phosphatase; 2) osteocalcin; 3) other noncollagen of bone matrix such as osteonectin, GLA-protein of the matrix, osteopontine and alpha 2-HS-glycoprotein; 4) Procollagenous and other collagenous peptides of the matrix (C terminal of type I procollagen and urinary elimination of non-dialysis hydroxyproline. Amongst the bone resorption markers studied are: 1) Calcium/creatinine urinary quotient; 2) Tartrate resistant acid phosphatase; 3) Urinary hydroxyproline; 4) Other substance derived from collagen disruption such as hydroxylysine glycoside, piridinolinic intermolecular bridges and the enzymatic activity of proline iminopeptidase. We endeavored to collect all the most important references on the matter, especially those relating to Paget's disease of the bone, primary hyperparathyroidism, tumoral hypercalcemia and postmenopausal osteoporosis.

Topics: Acid Phosphatase; Adult; Biomarkers; Bone Resorption; Child; Female; Follow-Up Studies; Humans; Hydroxyproline; Hypercalcemia; Hyperparathyroidism; Male; Neoplasms; Osteitis Deformans; Osteoporosis, Postmenopausal

Topics: Acid Phosphatase; Alkaline Phosphatase; Blood Glucose; Blood Sedimentation; Calcium; Calcium Isotopes; Ceruloplasmin; Glycosaminoglycans; Humans; Hydroxyproline; Magnesium; Osteitis Deformans; Phosphorus; Radionuclide Imaging; Strontium Isotopes; Uric Acid

Topics: Acid Phosphatase; Adult; Aged; Biomarkers; Bone Diseases, Metabolic; Bone Resorption; Breast Neoplasms; Female; Humans; Immunoassay; Isoenzymes; Middle Aged; Osteitis Deformans; Osteoporosis, Postmenopausal; Sensitivity and Specificity; Tartrate-Resistant Acid Phosphatase

We have examined the response of different biochemical bone turnover markers to intravenous pamidronate administration (15 mg for 5 days) in 14 patients with Paget's disease, on days 8, 15 and 30 after pamidronate treatment. Urinary parameters of bone resorption, free pyridinolines (Pyr) and hydroxyproline (OHP), as well as serum tartrate-resistant acid phosphatase (TRAP) were measured. Two serum biochemical osteoblastic markers, alkaline phosphatase (AP) and osteocalcin (OC), were also analysed. In addition, ionic calcium (Ca2+) was measured in blood, and parathyroid hormone and calcitriol were measured in serum. All the biochemical markers of bone resorption tested decreased throughout the study. TRAP levels decreased slowly, meanwhile Pyr decreased maximally, below OHP values on day 8. However, the latter were lowest and were lower than those of Pyr on days 15 and 30. AP serum values also decreased during the study. Conversely, OC serum levels increased on days 8 and 15, decreasing to baseline levels on day 30. Ca2+ blood levels decreased while PTH plasma levels increased at all times during the period studied. Calcitriol serum levels increased on day 15. In conclusion, intravenous pamidronate administration was found to modify several biochemical parameters of bone turnover, including Pyr. Moreover, the changes in these parameters were different in intensity and "time course" during the study.

Topics: Acid Phosphatase; Adult; Aged; Amino Acids; Biomarkers; Bone and Bones; Bone Resorption; Calcitriol; Diphosphonates; Female; Humans; Injections, Intravenous; Isoenzymes; Male; Middle Aged; Osteitis Deformans; Osteocalcin; Pamidronate; Tartrate-Resistant Acid Phosphatase

Clinical biochemical markers of bone turnover are usually increased in Paget's disease. However, the analysis of "new" markers, such as serum bone alkaline phosphatase (BAP), carboxy-terminal propeptide of type I procollagen (PICP), tartrate-resistant acid phosphatase (TRAP), telopeptide carboxy-terminal propeptide of type I collagen (ICTP), and urinary pyridinoline (PYR) and deoxipyridinoline (D-PYR), may improve the diagnostic efficacy and the evaluation of Paget's disease compared with conventional markers, such as serum total alkaline phosphatase (TAP) and urinary hydroxyproline (HYP). To evaluate the diagnostic accuracy and the changes of biochemical markers of bone turnover according to Paget's disease activity, we measured the levels of all these markers in three groups of pagetic patients classified according to their serum TAP activity: G-I, patients with serum TAP lower than 250 U/l (upper limit) (n = 15); G-II, patients with serum TAP between 251 and 500 U/l (n = 18); and G-III, patients with serum TAP greater than 501 U/l (n = 26). Serum TAP and BAP showed the highest diagnostic accuracy among the markers of bone formation with a sensitivity of 78% and 84%, respectively, when the specificity was 100%. Urinary PYR was the most sensitive marker of bone resorption. Also, urinary PYR showed the highest proportion of increased values in pagetic patients (73%) compared with urinary HYP (64%), urinary D-PYR (60%), serum ICTP (41%), or serum TRAP (39%). In pagetic patients with normal serum TAP activity (G-I), serum BAP concentration was increased in 60% of patients, and urinary PYR was increased in 40% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Amino Acids; Biomarkers; Bone Development; Bone Resorption; Collagen; Collagen Type I; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hydroxyproline; Male; Middle Aged; Osteitis Deformans; Peptide Fragments; Peptides; Procollagen

The addition of phosphate groups is an essential requirement for the proper functioning of cyclin and cyclin dependent kinase which control various stages in the mitotic division of cancer cells. Thus limiting the availability of phosphate is likely to interfere with the metabolism of rapidly growing malignant cells. The human hormone glucagon and the anti metabolite mithramycin reduce serum phosphate by increasing phosphaturia and are both very effective in treating Paget's disease of bone, a precancerous condition. In this disorder large doses of glucagon given intravenously relieve bone pain and cause serum phosphate and alkaline phosphatase as well as urine hydroxyproline to fall, indicating a marked reduction in bone turnover. A constant iv infusion of glucagon was given to each of three patients all of whom had secondary malignant bone deposits. Two of the patients had primary prostate cancer and one had a squamous cell lung tumour. All three patients had relief of bone pain and a fall in serum alkaline phosphatase. Serum acid phosphatase also fell in the two patients with prostate cancer. It is proposed that the marked drop in serum phosphate due to glucagon causes intracellular phosphate to fall. This in turn disrupts the addition and removal of phosphate groups essential for the proper functioning of cyclin and cyclin dependent kinase. These two proteins control the transition from G1 to S (DNA synthesis phase) and G2 to M (mitotic phase) in the dividing cycle of malignant cells. Depriving a tumour of an essential ingredient used in phosphorylation reactions will disrupt its growth. It is also proposed that, by the same mechanism, glucagon induced hypophosphataemia renders malignant cells more sensitive to established chemotherapeutic agents and radiation waves. If this hypothesis proves to be correct, lowering intracellular phosphate may become an useful tool in cancer therapy. However extensive studies are necessary to determine whether mitosis in cancer cells can be advantageously disrupted by glucagon induced hypophosphataemia.

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone and Bones; Carcinoma, Squamous Cell; Glucagon; Humans; Hydroxyproline; Hypophosphatemia, Familial; Insulin; Lung Neoplasms; Male; Mitosis; Models, Theoretical; Neoplasms; Osteitis Deformans; Phosphates; Phosphorylation; Prostatic Neoplasms

Paget's disease of bone (PDB) is characterized by abnormal osteoclasts with unique characteristics that include increased sensitivity of osteoclast progenitors to 1,25(OH)2 D3 , receptor activator of NF-κB ligand (RANKL), and TNF-α; increased osteoclast numbers; and increased expression of IL-6 and several transcription factors. We recently reported that measles virus nucleocapsid protein (MVNP) plays a key role in the development of these abnormal osteoclasts. MVNP can induce the pagetic osteoclast phenotype in vitro and in vivo in TRAP-MVNP transgenic mice. However, the molecular mechanisms by which MVNP generates pagetic osteoclasts have not been determined. TANK-binding kinase 1 (TBK1) and IκB kinase-ϵ (IKKϵ) are IKK family members that complex with MVNP and activate both IRF3 and NF-κB pathways. MVNP increases the amount of TBK1 protein in bone marrow monocytes (BMM). Interestingly, we found that RANKL increased TBK1 and IKKϵ early in osteoclast differentiation, suggesting a possible role in normal osteoclastogenesis. However, only TBK1 is further increased in osteoclasts formed by TRAP-MVNP BMM owing to increased TBK1 protein stability. TBK1 overexpression induced IL6 promoter reporter activity, and elevated endogenous IL6 mRNA and p65 NF-κB, TAF12, and ATF7 proteins in several cell lines. Overexpression of TBK1 was insufficient to induce pagetic osteoclasts from WT BMM but synergized with MVNP to increase pagetic osteoclast formation from TRAP-MVNP BMM. BX795 inhibition of TBK1 impaired MVNP-induced IL-6 expression in both NIH3T3 cells and BMM, and shRNA knockdown of Tbk1 in NIH3T3 cells impaired IL-6 secretion induced by MVNP and decreased TAF12 and ATF7, factors involved in 1,25(OH)2 D3 hypersensitivity of pagetic osteoclasts. Similarly, Tbk1 knockdown in BMM from TRAP-MVNP and WT mice specifically impaired development of the MVNP-induced osteoclast pagetic phenotype. These results demonstrate that TBK1 plays a critical role in mediating the effects of MVNP on osteoclast differentiation and on the expression of IL-6, a key contributor to the pagetic osteoclast phenotype.

Topics: Acid Phosphatase; Animals; HEK293 Cells; Humans; I-kappa B Kinase; Interleukin-6; Isoenzymes; Mice; NIH 3T3 Cells; Nucleocapsid Proteins; Osteitis Deformans; Protein Serine-Threonine Kinases; RANK Ligand; Tartrate-Resistant Acid Phosphatase; Tumor Necrosis Factor-alpha

In osteoprotegerin-deficient (OPG-/-) mice, osteoclast activity causes bone resorption to outpace bone formation, leading to the development of severe osteoporosis. Such mice are therefore useful for investigating the alveolar bone of patients with osteoporosis. Reveromycin A (RM-A) was recently identified as the unique agent acting on osteoclast activation. This study aimed to analyze the effect of RM-A on the orthodontic treatment of OPG-/- mice (a model of osteoporosis patients with high levels of bone turnover). We examined alveolar bone remodeling in OPG-/- and wild-type (WT) mice during continuous tooth movement. The orthodontic force was induced by means of a Ni-Ti closed-coil spring to move the maxillary first molar for 14 days. RM-A sodium salt (1 mg/kg) was administered intraperitoneally twice daily. In OPG-/- mice, the tooth movement distance was longer, alveolar bone resorption was enhanced, the osteoclast count was greater, and serum alkaline phosphatase and tartrate-resistant acid phosphatase levels were higher relative to those in WT mice. However, the administration of RM-A in OPG-/- mice reduced these parameters. We conclude that RM-A normalizes bone metabolism and loss of alveolar bone during continuous tooth movement in OPG-/- mice.

Topics: Acid Phosphatase; Alkaline Phosphatase; Alveolar Process; Animals; Biomarkers; Bone Density Conservation Agents; Bone Remodeling; Bone Resorption; Cell Count; Dental Alloys; Disease Models, Animal; Injections, Intraperitoneal; Isoenzymes; Male; Maxilla; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Knockout; Mutation; Nickel; Orthodontic Wires; Osteitis Deformans; Osteoclasts; Osteoporosis; Osteoprotegerin; Pyrans; Spiro Compounds; Tartrate-Resistant Acid Phosphatase; Titanium; Tooth Movement Techniques; X-Ray Microtomography

Osteoprotegerin (OPG) is a novel secreted member of the tumor necrosis factor receptor family which plays a crucial role in negative regulation of osteoclastic bone resorption. OPG-deficient (OPG-/-) mice develop severe osteoporosis caused by significant enhancement of bone resorption by osteoclasts. We investigated the effect of administering bisphosphonate on mandibular growth and development in OPG-/- mice. Eight-week-old male OPG-/- mice and wild-type (WT) mice were administered bisphosphonate (1.25 mg/kg body weight) intraperitoneally once every 3 days for 30 days. All bone formation-related parameters and bone resorption-related parameters were significantly lower in OPG-/- mice with bisphosphonate than in those without bisphosphonate. The volume of the whole condyle and the mandibular length in OPG-/- mice without bisphosphonate were significantly smaller than in WT mice without bisphosphonate. Bisphosphonate treatment of the OPG-/- mice resulted in an increase in the volume of the mandibular condyle and mandibular ramus length. In fact, the mandibular ramus length in OPG-/- mice with bisphosphonate was similar to the length in WT mice without bisphosphonate. Histologically, the surface irregularity of the mandibular condyle that was observed in the OPG-/- mice without bisphosphonate tended to be less marked in the OPG-/- mice with bisphosphonate, and the proportion of the area of the cartilage layer relative to the whole condyle was significantly larger in OPG-/- mice with bisphosphonate than in those without bisphosphonate. In conclusion, bisphosphonate treatment results in an increase in mandibular condylar dimensions and normalization of mandibular ramus growth.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Biomarkers; Bone Density Conservation Agents; Bone Resorption; Cell Count; Diphosphonates; Disease Models, Animal; Gene Silencing; Injections, Intraperitoneal; Isoenzymes; Male; Mandibular Condyle; Mice; Mice, Inbred C57BL; Mice, Knockout; Osteitis Deformans; Osteocalcin; Osteoclasts; Osteogenesis; Osteoprotegerin; Tartrate-Resistant Acid Phosphatase

Paget's disease is a condition of focal accelerated bone turnover. Electron-microscopy investigations of osteoclasts from pagetic lesions have identified nuclear inclusion bodies that have a similar appearance to viral nucleocapsid particles. Subsequently, RNA from several paramyxoviruses has been detected in pagetic tissue, and it was suggested that these viruses, in particular measles, might play a role in the etiology of Paget's disease. We have tested for measles virus sequences in osteoblasts and bone marrow cells collected from pagetic lesions and healthy bone.. Bone and bone marrow samples were taken from Paget's patients and control subjects, and cells were cultured from each of these tissues. RNA was extracted from 13 osteoblast cultures and 13 cultures of bone marrow cells derived from pagetic lesions, and from 26 and 23 control osteoblast and bone marrow cultures, respectively. These samples were sourced from 22 patients with Paget's disease and 31 controls. RT-PCR-nested PCR amplification was used for the detection of the genes for the measles nucleocapsid and matrix proteins.. Measles virus sequences were not detected in any of the pagetic or control samples. However, measles virus sequences were identified in samples of a measles virus culture isolate included as a positive control, and in a brain sample from a patient with subacute sclerosing panencephalitis, a condition associated with chronic measles infection.. The results of the study do not support the hypothesis that measles virus plays a role in the pathogenesis of Paget's disease.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Bone Marrow Cells; Female; Humans; Isoenzymes; Male; Measles virus; Middle Aged; Osteitis Deformans; Osteoblasts; Polymerase Chain Reaction; Receptor Activator of Nuclear Factor-kappa B; RNA, Viral; Tartrate-Resistant Acid Phosphatase

Osteoclast differentiation and activity, and hence bone loss, depend on two opposing cytokines. Receptor activator of NF-(kappa)B ligand (RANKL) produced by osteoblasts and T-cells stimulates, while osteoprotegerin inhibits. Both of these cytokines are found in serum. Our aim was to develop a functional assay for any factors present in human serum that can affect osteoclast differentiation and to assess whether any such factors vary in diseases in which bone loss occurs.. Using a culture model of osteoclast differentiation in the presence of macrophage colony stimulating factor and soluble RANKL, we have measured the effects of different human sera on osteoclast differentiation. The production of a marker enzyme for the osteoclast, tartrate-resistant acid phosphatase (TRAP), was used to follow osteoclast differentiation.. In general, human serum stimulates osteoclast differentiation as indicated by TRAP activity, but in patients with low bone density this stimulation was attenuated. Sera from 40 female subjects with low bone mineral density showed significantly lower TRAP cell differentiation activity than sera from the healthy female controls.. We describe a functional bio-assay for factors in human serum which can affect osteoclast differentiation. This assay may have application in monitoring the effects of therapy in bone disease.

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Aged, 80 and over; Animals; Biological Assay; Bone Density; Bone Diseases; Carrier Proteins; Cell Differentiation; Female; Humans; Isoenzymes; Macrophage Colony-Stimulating Factor; Male; Membrane Glycoproteins; Mice; Mice, Inbred BALB C; Middle Aged; Osteitis Deformans; Osteoclasts; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Tartrate-Resistant Acid Phosphatase

Pagetic osteoclasts (OCLs) are abnormal in size and contain paramyxoviral-like nuclear inclusions that cross-react with antibodies to measles virus (MV). However, the role that MV infection plays in Paget's disease is unknown, because no animal model of Paget's disease is available. Therefore, we targeted a cellular MV receptor, human CD46 (hCD46), to cells in the OCL lineage in transgenic mice using the mouse tartrate-resistant acid phosphatase (TRAP) gene promoter. In vitro infection of OCL precursors from hCD46 transgenic mice with MV significantly increased OCL formation in bone marrow cultures. The numbers of TRAP-positive mononuclear cells and CFU-GM, the earliest identifiable OCL precursor, were also significantly increased. MV-infected OCLs formed from hCD46 marrow were increased in size, contained markedly increased numbers of nuclei, and had increased bone-resorbing capacity per OCL compared with OCLs formed from marrow of nontransgenic littermates. Furthermore, IL-6 and 24-hydroxylase messenger RNA expression levels were increased in MV-infected hCD46 transgenic mouse bone marrow cultures. Treatment of MV-infected hCD46 marrow cultures with a neutralizing antibody to IL-6 blocked the increased OCL formation seen in these cultures. These data demonstrate that MV infection of OCL precursors results in OCLs that have many features of pagetic OCLs, that the enhanced OCL formation is in part mediated by increased IL-6 expression induced by MV infection, and suggest that the hCD46 transgenic mouse may be a useful model for examining the effects of MV infection on OCL formation in vivo.

Topics: Acid Phosphatase; Animals; Antigens, CD; Bone Marrow Cells; Bone Resorption; Cell Division; Humans; Interleukin-6; Isoenzymes; Measles; Membrane Cofactor Protein; Membrane Glycoproteins; Mice; Mice, Transgenic; Osteitis Deformans; Osteoclasts; Phenotype; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stem Cells; Tartrate-Resistant Acid Phosphatase

A characteristic feature of Paget's disease is an increase in the number of osteoclasts in bone. Osteoclasts are formed from mononuclear phagocyte precursors that circulate in the monocyte fraction of peripheral blood. These cells require the presence of RANK ligand (RANKL)-expressing osteoblastic cells and human macrophage colony-stimulating factor (M-CSF) to form osteoclasts in vitro. To determine the role of osteoclast differentiation from circulating precursors in Paget's disease, we cultured monocytes from Paget's patients and gender- and age-matched normal controls with no evidence of bone disease for up to 21 days in the presence of UMR 106 cells and various concentrations of M-CSF (1-25 ng/mL) and 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] (10(-10) to 10(-7) mol/L). Relative to controls, there was a significant increase in the extent of osteoclast differentiation from pagetic monocytes as assessed by expression of tartrate-resistant acid phosphatase (TRAP), vitronectin receptor (VNR), and lacunar bone resorption. Serial dilution experiments (2 x 10(5) to 2 x 10(2) cells/well) showed no difference in the concentration of osteoclast precursors in the peripheral blood. In Paget's patients with high serum alkaline phosphatase (sAP) levels, increased sensitivity to the osteoclastogenic effect of 1,25(OH)(2)D(3) was noted. Osteoclast differentiation did not occur when M-CSF was substituted by interleukin-6 (IL-6) and soluble IL-6 receptor (sIL-6R), and these factors did not stimulate osteoclast differentiation in the presence of M-CSF. In this in vitro coculture system, osteoclast formation was inhibited by osteoprotegerin in a dose-dependent manner. In the presence of RANKL (5-30 ng/mL) and M-CSF (25 ng/mL), osteoclast formation and bone resorption were significantly increased in cultures of monocytes from patients with high and low sAP levels as compared with normal controls. Our findings suggest that the increase in osteoclast numbers seen in Paget's disease results not from an increase in the number of circulating precursors in peripheral blood but rather from an increased sensitivity of osteoclast precursors to the humoral factors, 1,25(OH)(2)D(3) and RANKL, which regulate osteoclast formation.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Bone Resorption; Calcitriol; Carrier Proteins; Case-Control Studies; Cell Differentiation; Female; Hematopoietic Stem Cells; Humans; In Vitro Techniques; Interleukin-6; Macrophage Colony-Stimulating Factor; Male; Membrane Glycoproteins; Middle Aged; Osteitis Deformans; Osteoclasts; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Vitronectin

Tartrate-resistant acid phosphatase (TRAP) is a standard histochemical marker of differentiated osteoclasts and has been proposed as a serum/plasma marker for osteoclast activity. Enzyme assays have been described that show elevated TRAP enzyme activity in the serum or plasma of patient groups known to have increased bone metabolism. However, the poor stability of the enzyme and potential contribution from nonosteoclastic sources make it problematic to measure in patient samples. Immunoassays developed to measure TRAP in serum and plasma have yielded widely varying TRAP levels in both normal and disease states. It is not clear if this variability is caused by differences in assay calibration, antibody specificity, and/or TRAP instability. In this paper, we report that purified TRAP spiked into serum forms high molecular weight complexes. Complex formation results in greatly decreased TRAP enzyme activity and immunoreactivity. The complexing protein in serum has been identified as alpha2-macroglobulin (alpha2M). Similar complexes are observed in stored patient samples. In vitro studies with purified components show that TRAP binds to alpha2M primarily through noncovalent ionic interactions. Our results demonstrate that one mechanism of TRAP instability in serum is complex formation with alpha2M and suggest further that current TRAP enzyme and immunoassays may not accurately measure the circulating level of TRAP.

Topics: Acid Phosphatase; alpha-Macroglobulins; Biomarkers; Bone Diseases, Metabolic; Child; Enzyme Stability; Humans; Immunoenzyme Techniques; In Vitro Techniques; Isoenzymes; Macromolecular Substances; Molecular Weight; Osteitis Deformans; Osteoclasts; Protein Binding; Tartrate-Resistant Acid Phosphatase

The molecular mechanisms underlying Paget's disease and subsequent osteosarcoma formation are not well understood. In this study, we aim to delineate the function of the c-Fos oncogene in Paget's disease using transgenic mice, based on previous findings that c-Fos is highly expressed in Pagetic osteoclasts and that c-Fos is an essential gene for osteoclast differentiation and skeletal neoplasia. We have generated transgenic mice in which c-Fos is overexpressed specifically in osteoclasts using the tartrate-resistant acid phosphatase (TRAP) promoter, and five founder mice have been identified. All transgene-expressing animals developed severe bone remodeling lesions, some of which progressed to large bone tumors. Histopathologic analysis indicated that the lesions contained a marked increase in the number of osteoclasts that contained a large number of nuclei. Osteoclasts were identified by histochemical staining for TRAP and by in situ hybridization for matrix metalloproteinase-9 (MMP-9) expression. Moreover, transgenic osteoclasts, and in some cases, osteoblasts and chondrocytes, expressed high levels of c-Fos protein as judged by immunocytochemistry. This phenotype of increased osteoclast number and activity, together with an apparently high rate of bone turnover, resembles some characteristics of Paget's disease. These data therefore support an important function for c-Fos in the Pagetic phenotype, and further support the notion that this gene is important in osteoclastogenesis and in bone remodeling disorders.

Topics: Acid Phosphatase; Animals; Biomarkers; Bone and Bones; Chondrocytes; In Situ Hybridization; Isoenzymes; Matrix Metalloproteinase 9; Mice; Mice, Transgenic; Osteitis Deformans; Phenotype; Proto-Oncogene Proteins c-fos; Tartrate-Resistant Acid Phosphatase

Osteoectasia with hyperphosphatasia is a rare skeletal disorder, characterised by demineralisation and expansion of tubular bones and elevated serum alkaline phosphatase. We present a girl diagnosed as having osteoectasia with hyperphosphatasia who had swelling of phalanges of both hands and motor retardation. She was treated with synthetic human calcitonin. Clinical and radiological findings showed remarkable improvement after 2 years' treatment.

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone and Bones; Calcitonin; Female; Humans; Infant; Osteitis Deformans; Radiography

To evaluate the relationship between biochemical markers of bone turnover and bone scan indices of disease activity, as well as to analyze their variations based on skeletal involvement, in Paget's disease.. Serum samples were obtained from 51 patients with Paget's disease to determine the levels of total alkaline phosphatase (total AP), bone alkaline phosphatase (bone AP), propeptide carboxyterminal of type I procollagen (PICP), propeptide aminoterminal of type I procollagen (PINP), osteocalcin, tartrate-resistant acid phosphatase, and telopeptide carboxyterminal of type I collagen. Urine samples were analyzed for levels of hydroxyproline (HYP), pyridinoline (PYR), deoxypyridinoline (DPYR), C-terminal telopeptide of type I collagen (CTx), and N-terminal telopeptide of type I collagen (NTx). In addition, 2 semiquantitative scintigraphic indices, disease activity (AI) and disease extent (EI), were obtained. Pagetic skeletal locations were evaluated individually, with special attention to skull involvement.. All biochemical markers correlated with the AI and the EI. Serum PINP, bone AP, and total AP showed the highest proportions of increased values among the bone formation markers (94%, 82%, and 76%, respectively). Among the bone resorption markers, urinary NTx showed the highest proportion of increased values in patients with Paget's disease (96%), compared with PYR (69%), DPYR (71%), CTx (65%), and HYP (64%). In patients with mild disease activity, serum PINP was the marker with the highest proportion of increased values (71%). In contrast, serum PICP and urinary CTx were the most discriminative markers for skull involvement. Except for higher values for most of the biochemical markers of bone turnover in flat bones, no major differences in other skeletal locations were observed.. The determination of serum PINP as a marker of bone formation and urinary NTx as a marker of bone resorption provided the best biochemical profile to ascertain the extent and activity of Paget's disease. In patients with skull involvement, serum PICP and urinary CTx were shown to be the most discriminative markers.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Biomarkers; Bone and Bones; Bone Resorption; Collagen; Female; Humans; Male; Middle Aged; Osteitis Deformans; Osteocalcin; Radionuclide Imaging; Tartrates

The etiology and pathophysiology of Paget's disease of bone are not yet entirely defined. There is evidence suggesting the participation of the immune system in the pathophysiology of this disease. Hence, we examined T cell mitogenic proliferation, NK cell activity, T cell subsets, interleukin-1 (IL-1), and interleukin-6(IL-6) production by peripheral mononuclear cells and IL-6 levels in the peripheral blood sera of 17 Paget's patients aged (74.5 +/- 2.4 years) and of 17 elderly control subjects (74.7 +/- 2.2 years). Pagetic patients were found to have immunological parameters not significantly different from those of the elderly control group. Moreover, the results obtained from Paget's patients with the active form of the disease did not differ from those of patients with inactive disease. Therefore, at least on the basis of the parameters used in this study, it is possible to conclude that the cellular immunity of Paget's patients is not different from that of elderly control subjects and that the role of IL-1 and IL-6 in this disease should be reviewed.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Alkaline Phosphatase; Calcium; CD4-CD8 Ratio; Cytotoxicity, Immunologic; Female; Humans; Immunity, Cellular; Interleukin-1; Interleukin-6; Killer Cells, Natural; Leukocyte Count; Lymphocyte Activation; Lymphocyte Count; Male; Middle Aged; Osteitis Deformans; Phosphorus; Reference Values; T-Lymphocyte Subsets; T-Lymphocytes

Collagen type 1 represents more than 90% of bone matrix. Therefore, quantitation of collagen crosslinks, such as deoxypyridinoline, can provide information on bone resorption degree. An evaluation was made of deoxypyridinoline as well as other bone markets, such as alkaline phosphatase, tartrate resistant acid phosphatase, and hydroxyproline in patients with the diagnosis of osteoporosis. Paget's disease, hyperthyroidism, and chronic renal failure on haemodialysis or not. Deoxypyridinoline levels were significantly increased in patients with osteoporosis, Paget's disease, and hyperthyroidism. Hydroxyproline levels were increased in patients with Paget's disease, and tartrate resistant acid phosphatase was increased in all the entities studied. Deoxypyridinoline can be a more sensitive marker than hydroxyproline, with some advantages, such as its quantitation in a urine specimen and its high bone specificity. In patients with renal failure, tartrate resistant acid phosphatase was the only biochemical marker of bone resorption with increased levels.

Topics: Acid Phosphatase; Adult; Alkaline Phosphatase; Amino Acids; Biomarkers; Bone Resorption; Female; Humans; Hydroxyproline; Hyperthyroidism; Kidney Failure, Chronic; Male; Middle Aged; Osteitis Deformans; Osteoporosis; Sensitivity and Specificity

The detection of virus in osteoclasts from Pagetic patients is now well known, but it has yet to be shown convincingly that the presence of virus in Pagetic osteoclasts influences their behaviour. In this study, osteoclasts from embryonic chick tibiae were infected with canine distemper virus or measles virus and compared with mock-infected controls. Infection was confirmed using virus-specific fluorescent antibodies. It was found that virus infection did not alter osteoclast morphology or tartrate-resistant acid phosphatase (TRAP) activity. Both infected and mock-infected osteoclasts produced resorption pits on bovine bone slices; these could be divided into two distinct size classes with a computer-based measuring system. Virus infection significantly increased the proportion of the larger size class of resorption pit. These results suggest that virus infection can increase bone resorption by osteoclasts, lending further support to the hypothesis that viruses play a role in Paget's disease of bone.

Topics: Acid Phosphatase; Animals; Bone Resorption; Cell Culture Techniques; Chick Embryo; Distemper; Distemper Virus, Canine; Fluorescent Antibody Technique; Isoenzymes; Measles; Osteitis Deformans; Osteoclasts; Tartrate-Resistant Acid Phosphatase

Recent evidence has implicated canine distemper virus (CDV) as a possible aetiologic agent in Paget's disease of bone and the canine bone disorder, metaphyseal osteopathy. We have therefore examined the effects of CDV on the formation of multinucleated osteoclast-like cells in cultures of canine bone marrow mononuclear cells. Marrow cells from a distemper-infected dog and from five uninfected dogs were cultured in the presence of 1 alpha, 25-(OH)2 vitamin D3 and the number of tartrate resistant acid phosphatase positive multinucleated cells (MNCs) was determined. The presence of calcitonin (CT) receptors was confirmed by autoradiography with 125I-labeled human CT. Cultures from the distemper-infected dog contained a higher level of MNCs than those from the normal dogs. The in vitro addition of CDV to the cultures from all the dogs produced a dose-dependent increase in the number of MNCs, and an increase in size of these cells in the cultures from the infected dog. Cells infected with CDV were hyperresponsive to 1 alpha,25-(OH)2 vitamin D3. The presence of the virus in the relevant samples was confirmed using molecular techniques. In situ hybridization studies also revealed a significant increase in the level of infection following in vitro addition of the virus to the culture from the distemper-infected dog, suggesting that further infection had taken place. Resorption pits were formed on bone slices, although the number of pits was not significantly altered by viral infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acid Phosphatase; Animals; Autoradiography; Bone Marrow; Bone Marrow Cells; Bone Resorption; Calcitriol; Cells, Cultured; Disease Models, Animal; Distemper Virus, Canine; Dogs; Giant Cells; Humans; In Situ Hybridization; Isoenzymes; Osteitis Deformans; Osteoclasts; Polymerase Chain Reaction; Receptors, Calcitonin; Tartrate-Resistant Acid Phosphatase

We examined the response of different biochemical markers of bone resorption to bisphosphonate therapy (400 mg of etidronate daily for 6 months) in mild Paget disease (n = 14). Urinary markers included hydroxyproline (OHP), total (T) and free (F) pyridinolines (Pyds) determined by HPLC, immunoreactive FPyds, immunoreactive TPyds, and the N- and C-terminal telopeptides of type I collage (NTx, CL). Serum measurements included tartrate-resistant acid phosphatase (TRAcP) and the C-terminal telopeptide of type I collagen (ICTP). ICTP and TRAcP showed a minimal response to therapy (% change at 6 months, -13.1 +/- 6.8 and -6.7 +/- 3.4, respectively). The response was greatest for urinary telopeptides (NTx and CL; % change -75.7 +/- 7.5 and -73.4 +/- 8.9, respectively). The response was somewhat greater for TPyds than for FPyds. We conclude that: (a) ICTP and TRAcP are unreliable indicators of changes in bone turnover; (b) oligopeptide-bound Pyds and telopeptide fragments of type I collagen in urine show a somewhat greater response to therapy than do FPyds and may be more sensitive indicators of bone resorption; and (c) as yet no evidence suggests that these markers are substantially better predictors of the clinical response to therapy than serum total alkaline phosphatase or urinary OHP. There are several problems with the interpretation of these measurements in Paget disease, and the clinical utility of these measurements remains uncertain.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Amino Acids; Biomarkers; Bone Resorption; Chromatography, High Pressure Liquid; Collagen; Drug Resistance; Etidronic Acid; Female; Humans; Hydroxyproline; Male; Middle Aged; Osteitis Deformans; Peptide Fragments; Tartrates; Testosterone

Bisphosphonates are known to be potent inhibitors of osteoclast activity and their only clinically relevant effect in the short-term is the selective inhibition of bone resorption. The purpose of this study was to compare the response to the intravenous administration of two bisphosphonates, clodronate and alendronate, of several biochemical markers of bone resorption, including tartrate-resistant acid phosphatase (TRAP) and cross-linked carboxyterminal telopeptide of collagen I (ICTP) in serum and hydroxyproline (OHP), free pyridinium cross-links (Pyr), and cross-linked N-telopeptides of collagen I (NTx) in urine. The study was carried out on 11 osteoporotic and 12 Pagetic subjects of both sexes, treated with clodronate (600 mg/day for 2 days) or alendronate (5 mg/day for 2 days), and monitored for 28 days after bisphosphonate administration. All the urinary markers of bone resorption showed a prompt decline after bisphosphonates, with maximum reductions after 7-14 days: Pyr decreased by 43% +/- 9% and 42% +/- 22% (mean +/- SD), respectively in osteoporotic and pagetic subjects, OHP by 51% +/- 14% and 51% +/- 20%, and NTx by 55% +/- 15% and 65% +/- 26%. In the osteoporotic group, the urinary markers began to increase again at 30 days, though still remaining well below the basal level, whereas in the pagetic group, the excretion of all markers remained depressed until the end of the observation period. The reduction of NTx was significantly greater than that of Pyr and OHP in pagetic patients (P < 0.05) and tended to be greater than that of Pyr in osteoporotic patients (p = 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Alendronate; Amino Acids; Biomarkers; Bone and Bones; Bone Resorption; Clodronic Acid; Collagen; Collagen Type I; Diphosphonates; Female; Humans; Hydroxyproline; Injections, Intravenous; Male; Middle Aged; Osteitis Deformans; Osteoporosis; Peptides; Time Factors

Beta2-microglobulin has been observed to behave as a biological marker of bone remodeling. We measured beta2-microglobulin and tartrate-resistant acid phosphatase (TRAP), a specific biological marker of bone remodeling, in 225 women: healthy premenopausal controls, healthy postmenopausal control, and patients with diseases characterized by enhanced bone turnover (postmenopausal osteoporosis, primary hyperparathyroidism, primary hyperthyroidism, polyostotic Paget's bone disease), and in other Paget's group before and after calcitonin treatment. Beta2-microglobulin levels differed significantly between the healthy premenopausal women (n = 20) compared with all the other groups. However, beta2-microglobulin levels did not differ significantly between healthy postmenopausal women (n = 38) and patient's with Paget's bone disease (n = 40)(P = 0.5095), or between women with postmenopausal osteoporosis (n = 30) and women with hyperthyroidism (n = 20)(P = 0.7890). TRAP concentrations differed significantly in all the groups paired except for women with Paget's bone disease and women with either hyperparathyroidism or hyperthyroidism (P = 0.5179 and 0.6993, respectively); likewise, TRAP levels did not differ significantly between the women with hyperparathyroidism and those with hypothyroidism (P = 0.7804). After calcitonin treatment, there was a 22% increase in beta2-microglobulin, a 17% decrease in TRAP, and a 39% decrease in alkaline phosphatase, all of which were significant at P < 0.0001. Our findings indicate that serum beta2-microglobulin, like osteocalcin, behaves as a biological marker of remodeling in a number of diseases with enhanced bone remodeling but not in Paget's bone disease.

Topics: Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; beta 2-Microglobulin; Biomarkers; Bone Remodeling; Female; Humans; Hyperparathyroidism; Hyperthyroidism; Middle Aged; Osteitis Deformans; Osteoporosis, Postmenopausal; Regression Analysis

On the basis of earlier findings of increased serum beta 2-microglobulin concentration in women with postmenopausal osteoporosis, we decided to study serum beta 2-microglobulin concentration in other bone diseases. In 28 patients with untreated Paget's bone disease, serum beta 2-microglobulin concentration was normal (1.49 +/- 0.41 mg/liter versus 1.36 +/- 0.21 mg/liter in 42 control subjects, P = ns), a finding that contradicts reports in the literature. We found that serum beta 2-microglobulin concentration was related negatively and significantly (r2 = -0.154, P = 0.0354) with serum total alkaline phosphatase concentration, but not with serum tartrate-resistant acid phosphatase concentration (p = ns). Urinary elimination of beta 2-microglobulin was lower in the patients with Paget's disease than in the controls (34 +/- 28 versus 120 +/- 21 mg/liter, P < 0.001). These findings suggest that beta 2-microglobulin behaves similarly to osteocalcin (BGP) in Paget's bone disease and that its concentration remains within normal levels perhaps because of the rate of reuptake of beta 2-microglobulin in bone neoformation.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; beta 2-Microglobulin; Humans; Middle Aged; Osteitis Deformans; Regression Analysis

Nuclear inclusions, identical to those characteristic of Paget's disease of bone, were observed in giant cells in four of eight cases of primary oxalosis. The giant cells containing nuclear inclusions were directly involved in phagocytosis of large oxalate crystals in the context of typical foreign body granulomas in the bone marrow. Cytochemically, all of them exhibited strong tartrate-resistant acid phosphatase activity, and a proportion of them also tartrate-resistant acid ATPase. The inclusions consisted of typical arrays of filamentous material as described in Paget's disease, admixed with variable proportions of electron-dense material closely reminiscent of nucleolar pars fibrillaris and fibrillary centres. These data indicate: (a) the occurrence of Paget-like inclusions in a bone disease unrelated to Paget's disease, not causally related to viral infection, and resulting from an inborn metabolic derangement; and (b) the occurrence of Paget-like inclusions in foreign body giant cells as opposed to osteoclasts. We suggest that the occurrence of paramyxovirus-like nuclear inclusions in either osteoclasts or giant cells may represent an epiphenomenon of cell fusion and giant cell formation whenever appropriate stimuli act on latently infected precursor cells. Furthermore, our data suggest that nucleoli may represent the specific site of virus-like inclusion formation.

Topics: Acid Phosphatase; Adenosine Triphosphatases; Adolescent; Adult; Bone and Bones; Cell Nucleus; Crystallization; Giant Cells, Foreign-Body; Humans; Hyperoxaluria; Immunohistochemistry; Microscopy, Electron; Osteitis Deformans; Osteoclasts; Oxalates; Paramyxoviridae; Respirovirus Infections; Retrospective Studies

Tartrate-resistant acid phosphatase (TrACP) is abundant in alveolar macrophages, suggesting that these cells might contribute to the activity of this isoenzyme in sera of patients with conditions characterized by activation of alveolar macrophages. TrACP was therefore measured in patients with pulmonary sarcoidosis and cryptogenic fibrosing alveolitis and compared with values in controls. Since osteoclasts are known to be the main source of TrACP in serum several indices of bone-turnover were also measured: serum bone-specific alkaline phosphatase and urine hydroxyproline:creatinine ratios. Patients with Paget's disease of bone constituted a reference group presenting increased bone turnover. TrACP was not significantly higher in the lung-disease groups than in controls, although there was a strong positive correlation with angiotensin-converting enzyme in pulmonary sarcoidosis. As expected, TrACP activity was elevated together with the other indices of bone turnover in Paget's disease. It is unlikely that TrACP from alveolar macrophages contributes significantly to serum acid phosphatase activity in lung disease.

Topics: Acid Phosphatase; Adult; Aged; Female; Humans; Isoenzymes; Lung Diseases; Macrophage Activation; Male; Middle Aged; Osteitis Deformans; Pulmonary Fibrosis; Sarcoidosis; Tartrate-Resistant Acid Phosphatase; Tartrates

The study was carried out to evaluate the clinical validity and usefulness of serum tartrate-resistant acid phosphatase (TRAP) activity determined using an improved spectrophotometric assay. Enzyme activity was measured in 84 normal subjects and in 109 patients with common metabolic bone diseases. Mean values of serum TRAP activity in male subjects (n = 19; 10.4 +/- 2.15 U l-1) were not significantly different from those found in female subjects (n = 65; 10.8 +/- 1.8 U l-1). In the latter group mean values were significantly raised in post-menopausal subjects (10.5 +/- 2.0 U l-1; p less than 0.01) compared with mean values in pre-menopausal women (8.45 +/- 1.8 U l-1). We found a significant inverse correlation between serum TRAP activity values and bone mineral density (BMD) measured both at an ultradistal radial point (n = 33, r = -0.506; p less than 0.01), and at the lumbar spine (n = 57, r = -0.261; p less than 0.05). Mean serum TRAP activity values in patients with metabolic bone diseases were: primary hyperparathyroidism, n = 30: 14.2 +/- 4.89 U l-1, p less than 0.001 vs normal subjects; chronic maintenance haemodialysis, n = 19: 17.4 +/- 6.7, p less than 0.001; metastatic cancer, n = 13: 21.2 +/- 6.3, p less than 0.001; post-surgical hypoparathyroidism, n = 10: 9.9 +/- 1.8, NS; involutional osteoporosis, n = 20: 12.5 +/- 2.3 p less than 0.001; Paget's disease, n = 10: 16.8 +/- 3.5, p less than 0.001; osteomalacia, n = 7: 19.5 +/- 3.31, p less than 0.001.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acid Phosphatase; Adult; Aging; Bone Density; Bone Diseases, Metabolic; Bone Remodeling; Female; Humans; Hyperparathyroidism; Male; Menopause; Middle Aged; Osteitis Deformans; Osteomalacia; Osteoporosis; Osteoporosis, Postmenopausal; Spectrophotometry; Tartrates

Tartrate resistant acid phosphatase (TRAP) has been proposed as a new biochemical marker for bone resorption. We have compared this new marker, TRAP, with the classical biochemical markers of bone remodelling, serum alkaline phosphatase (sAP), serum osteocalcin (sBGP), and with the urinary hydroxyproline/creatinine ratio (uOHProl/creatinine), a routine marker of bone resorption. Serum TRAP was significantly higher in pagetic patients (n = 43) than in control subjects (n = 12) (13.02 +/- 4.7 vs 5.48 +/- 1.31 IU/L, P less than 0.001) and a significantly positive linear correlation was found between the sTRAP and uOHProl/creatinine ratio (y = 0.0051x - 0.0069, r = 0.82, P less than 0.001), between sTRAP and sAP (y = 19.3x - 85.0, r = 0.71, P less than 0.001) and also between sTRAP and sBGP (y = 0.02x + 2.23, r = 0.52, P less than 0.01). Serum TRAP levels were higher than the upper limit of normality in all our pagetic patients except for two, whose uOHProl/creatinine levels were in the normal range. We conclude that (1) sTRAP could be a parameter as sensitive as uOHProl/creatinine in the diagnosis of Paget's disease; (2) sTRAP and uOHProl/creatinine are both good markers of bone resorption; (3) the correlation found between sTRAP and formation markers (sAP and sBGP) makes sTRAP a marker of disease activity in Paget's disease of bone; (4) the assay of sTRAP is easier, faster, and of lower cost than the urinary hydroxyproline determination. We suggest that sTRAP determination could be used as a routine marker of bone resorption in Paget's disease of bone, as is the case with uOHProl determination.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Biomarkers; Bone Resorption; Creatinine; Female; Humans; Hydroxyproline; Male; Middle Aged; Osteitis Deformans; Osteocalcin; Tartrates

16 patients with a Paget's disease at the age of 51--80 years were treated by synthetic salmon calcitonine in a dosis of 20 mcg (80 MRCU/die). 14 patients could be observed for a longer time. In all cases there was a statically significant decrease of the increased alkaline serum phosphatase. The excretion of hydroxyproline in the collected urine had a decreasing tendency. Other laboratory parameters as calcium, phosphatase and acid phosphatase in the serum and the excretion of calcium and phosphate in the urine were not significant influenced by therapy. The patients felt subjective a clear improvement of the bone pains. After a six month-treatment the dosis was reduced (each 2--7 days 20 mcg salmon calcitonin sc). There was observed a rebehaviour of the subjective symptoms and an increase of the alkaline serum phosphatase, which did not reach the unitial values before the beginning of treatment. Calcitonine is an effective substance for the treatment of an active Paget's disease.

Topics: Acid Phosphatase; Aged; Calcitonin; Calcium; Female; Humans; Long-Term Care; Male; Middle Aged; Osteitis Deformans; Phosphorus; Proline

The method of Hillmann, in which hydrolysis of alpha-naphthyl phosphate by acid phosphatase is coupled to the formation of an alpha-naphthol-Fast Red TR azo-compound, has been adapted for use with the LKB Produkter AB 8600 reaction rate analyzer. Factors which affect the reproducibility of the method are described and its performance is shown to be superior to that of a manual phenyl-phosphate procedure.

Topics: Acid Phosphatase; Autoanalysis; Evaluation Studies as Topic; Female; Humans; Hydrogen-Ion Concentration; Indicators and Reagents; Kinetics; Male; Osteitis Deformans; Prostatic Neoplasms; Spectrophotometry

Starting from the fact that an ultrastructural cytochemical study of the Giant-Cell Tumour demonstrated the presence of a large amount of lysosomic acid phosphatase in the tumour cells, an attempt was made to evidence the presence of this enzyme in the serum of patients bearing such a type of bone tumor. Acrylamide gel electrophoresis of the serum allowed one to separate a number of isoenzyme with acid phosphatase activity and to characterize at least two bands different from those secreted by prostate, blood platelets, liver or spleen. The comparison between zymograms of normal and pathological sera, more particularly in Paget disease, led to consider that these two bands had an osteoclastic origin. Besides, these bands vanish after tumor eradication. Acrylamide gel electrophoresis of serum provides therefore a means to support the preoperative diagnosis of Giant-Cell Tumor and, eventually, to detect an early recurrence of the disease.

Topics: Acid Phosphatase; Electrophoresis, Polyacrylamide Gel; Giant Cell Tumors; Humans; Isoenzymes; Lysosomes; Osteitis Deformans; Osteoclasts

The laboratory investigation of cases of Paget's disease has revealed results of three types :--small increases in the sedimentation rate, in the ceruloplasmin level, in the average corpuscule volume, and in uricaemia. These changes are of little practical value;--a considerable increase in the common stocks and in the turn-over of calcium, a frequently negative assessment with a parathyroid hormone level at the lower limit of normality. The levels of calcaemia and calciuria, little changed on average, may increase slightly after hospitalization. The use of these parameters is valuable but they are sometimes difficult to interpret;--an increase in the levels of alkaline phosphatases and of urinary hydroxyproline, in relation to the extent and the activity of the disease, and also of certain parameters of calcium-45 and of quantitative histology. A statistical study of the spontaneous evolution of hydroxyprolinuria in 50 patients with Paget's disease who were not treated for less than 3 years, allowed the authors to establish in what conditions a change induced by calcitonin or mithramycin is significant.

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Resorption; Calcitonin; Calcium; Follow-Up Studies; Humans; Hydroxyproline; Osteitis Deformans; Osteoblasts; Phosphorus; Plicamycin

Topics: Acid Phosphatase; Aged; Biopsy; False Negative Reactions; Humans; Male; Middle Aged; Neoplasm Metastasis; Osteitis Deformans; Phosphates; Prostatic Neoplasms; Radiography; Radionuclide Imaging; Technetium

Topics: Acid Phosphatase; Aged; Biopsy; Bone and Bones; Bone Resorption; Calcium; Calcium Radioisotopes; Ethanol; Female; Follow-Up Studies; Humans; Hydroxyproline; Kinetics; Male; Middle Aged; Organophosphonates; Organophosphorus Compounds; Osteitis Deformans; Phosphorus; Time Factors

Topics: Acid Phosphatase; Adolescent; Alkaline Phosphatase; Arm; Bone and Bones; Bone Diseases, Developmental; Child; Child, Preschool; Collagen; Diagnosis, Differential; Female; Haversian System; Humans; Infant; Infant, Newborn; Leg; Male; Metabolism, Inborn Errors; Osteitis Deformans; Pelvic Bones; Radiography; Skull; Syndrome

Topics: Acid Phosphatase; Alkaline Phosphatase; Electrophoresis; Humans; Osteitis Deformans

Topics: Acid Phosphatase; Alkaline Phosphatase; Blood Pressure; Calcium; Cardiac Output; Heart Rate; Humans; Male; Middle Aged; Osteitis Deformans; Paraplegia; Phosphates; Spinal Diseases

Topics: 5'-Nucleotidase; Acid Phosphatase; Adenine Nucleotides; Alkaline Phosphatase; Blood; Bone and Bones; Clinical Enzyme Tests; Diagnosis; Glycerophosphates; Histidine; Humans; Intestines; Liver Neoplasms; Magnesium; Nickel; Nucleotidases; Osteitis Deformans; Protein Tyrosine Phosphatases

Topics: Acid Phosphatase; Bone Diseases; Bone Neoplasms; Clinical Enzyme Tests; Diagnosis, Differential; Gaucher Disease; Humans; Hyperparathyroidism; Male; Osteitis Deformans; Osteitis Fibrosa Cystica; Osteogenesis Imperfecta; Osteopetrosis; Osteosclerosis; Prostatic Neoplasms