acid-phosphatase and Bone-Diseases

Chronic renal failure is often associated with bone disorders, including secondary hyperparathyroidism, aluminum-related low-turnover bone disease, osteomalacia, adynamic osteopathy, osteoporosis, and skeletal beta2-microglobulin amyloid deposits. In spite of the enormous progress made during the last few years in the search of noninvasive methods to assess bone metabolism, the distinction between high- and low-turnover bone diseases in these patients still frequently requires invasive and/or costly procedures such as bone biopsy after double tetracycline labeling, scintigraphic-scan studies, computed tomography, and densitometry. This review is focused on the diagnostic value of several new serum markers of bone metabolism, including bone-specific alkaline phosphatase (bAP), procollagen type I carboxy-terminal extension peptide (PICP), procollagen type I cross-linked carboxy-terminal telopeptide (ICTP), pyridinoline (PYD), osteocalcin, and tartrate-resistant acid phosphatase (TRAP) in patients with chronic renal failure. Most of the observations made by several groups converge to the conclusion that serum bAP is the most sensitive and specific marker to evaluate the degree of bone remodeling in uremic patients. Nonetheless, PYD and osteocalcin, in spite of their retention and accumulation in the serum of renal insufficient patients, are also excellent markers of bone turnover. The future generalized use of these markers, individually or in combination with other methods, will undoubtedly improve the diagnosis and the treatment of the complex renal osteodystrophy.

Topics: Acid Phosphatase; Alkaline Phosphatase; Amino Acids; beta 2-Microglobulin; Biomarkers; Bone Diseases; Bone Remodeling; Collagen; Collagen Type I; Glycation End Products, Advanced; Humans; Integrin-Binding Sialoprotein; Isoenzymes; Osteocalcin; Peptide Fragments; Peptides; Procollagen; Sialoglycoproteins; Tartrate-Resistant Acid Phosphatase; Uremia

A review is given summarizing the present knowledge of bone turnover markers with special emphasis on biological, preanalytical and technical criteria in the proper judgement of efficacy and limitations of the methods employed. The marker substances may be either measures of bone formation or bone resorption. Markers of bone formation are bone alkaline phosphatase, osteocalcin and the carboxyl-terminal propeptide of procollagen type I. Bone alkaline phosphatase has proved to be superior to total alkaline phosphatase activity with respect to diagnostic sensitivity and specificity. Immunochemical techniques for measuring bone alkaline phosphatase show a cross-reactivity of 14-20% with liver alkaline phosphatase. However, this does not compromise the clinical usefulness of these assays except for patients with severe liver diseases. Osteocalcin is strictly bone-specific but shows numerous disadvantages with respect to apparent instability and discordant results as obtained by different methods; however, in certain diagnostic situations (corticosteroid-induced osteopenia, absence of destroyed bone architecture) osteocalcin may serve as a sensitive bone turnover marker. The carboxyl-terminal propeptide of procollagen type I generally shows low discriminating power in the diagnosis of bone diseases. The urinary excretion of pyridinium "cross-links' has been carefully evaluated so far with respect to analytical performance and clinical usefulness. This marker may be a substitute for 4-hydroxyproline measurements as the method of choice for assessment of bone resorption. There are other degradation products from the telopeptide regions of bone-derived collagen type I which are excreted into the urine (N-telopeptides, CrossLapsTM); these analytes are promising tools in the assessment of bone resorption but require further evaluation, in particular with respect to their extraskeletal clearance and putative origin outside bone. Moreover, their clinical usefulness may vary depending on the patient group examined. In contrast, the serum concentration of the cross-linked telopeptide region of collagen type I seems to lack both diagnostic specificity and sensitivity in the majority of patient groups. Tartrate-resistant acid phosphatase (as determined by the presently available methods) cannot be recommended as a routine tool for assessment of bone resorption.

Topics: Acid Phosphatase; Adult; Alkaline Phosphatase; Amino Acid Sequence; Animals; Biomarkers; Bone Diseases; Bone Remodeling; Collagen; Collagen Type I; Female; Humans; Male; Menopause; Molecular Sequence Data; Osteocalcin; Osteonectin; Peptides; Pyridinium Compounds; Sialoglycoproteins; Tartrates

The measurement in blood of bone proteins is an important adjunct to imaging procedures for clinical assessment of the skeleton. The discovery of new bone proteins and their structural characterization has led to immunochemical procedures of improved sensitivity and specificity for their quantification. An appreciation of the advantages and disadvantages of these evolving methodologies will assist in their clinical application.

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone and Bones; Bone Diseases; Calcium-Binding Proteins; Collagen; Extracellular Matrix Proteins; Humans; Matrix Gla Protein; Osteocalcin

Topics: Acid Phosphatase; Blood Platelet Disorders; Bone and Bones; Bone Diseases; Breast Neoplasms; Electrophoresis, Polyacrylamide Gel; Erythrocytes; Female; Hematologic Diseases; Humans; Isoenzymes; Leukemia; Leukocytes; Lipidoses; Male; Primary Myelofibrosis; Prostate; Prostatic Neoplasms; Spleen; Thromboembolism

Topics: Acid Phosphatase; Adult; Bone Diseases; Cerebrosides; Epilepsy, Temporal Lobe; Gaucher Disease; Graft Rejection; Graft vs Host Reaction; Humans; Intellectual Disability; Kyphosis; Lymphopenia; Male; Postoperative Complications; Radionuclide Imaging; Spleen; Technetium; Thrombocytopenia; Transplantation, Homologous

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Development; Bone Diseases; Chromosome Aberrations; Chromosome Disorders; Humans; Japan

Spondyloenchondrodysplasia (SPENCD) is a rare skeletal dysplasia, characterized by metaphyseal lesions, neurological impairment and immune dysregulation associated with lupus-like features. SPENCD is caused by biallelic mutations in the ACP5 gene encoding tartrate-resistant phosphatase. We report on a child, who presented with spasticity, multisystem inflammation, autoimmunity and immunodeficiency with minimal metaphyseal changes due to compound heterozygosity for two novel ACP5 mutations. These findings extend the phenotypic spectrum of SPENCD and indicate that ACP5 mutations can cause severe immune dysregulation and neurological impairment even in the absence of metaphyseal dysplasia.

Topics: Acid Phosphatase; Autoimmune Diseases; Autoimmunity; Bone Diseases; Child; Female; Humans; Immunologic Deficiency Syndromes; Inflammation; Isoenzymes; Magnetic Resonance Imaging; Muscle Spasticity; Mutation; Osteochondrodysplasias; Tartrate-Resistant Acid Phosphatase; Tomography, X-Ray Computed

Gaucher disease (GD) is a lysosomal storage disorder characterized by accumulation of glucosylceramide in macrophages, so-called Gaucher cells, as a result of a deficiency of the lysosomal enzyme glucocerebrosidase. Bone complications are an important cause of morbidity of GD and are thought to result from imbalance in bone remodeling. Bone manifestations among GD patients demonstrate a large variation including increased osteoclastic bone resorption, low bone formation and osteonecrosis. The purpose of the current case series is to describe the histological features observed in undecalcified bone samples, obtained from three GD patients, and evaluate the relationship with clinical features in these patients. Bone fragments were obtained from three adult type 1 GD patients with variable degrees of bone disease during orthopedic surgery. Specimens were embedded without prior decalcification in methylmethacrylate and prepared for histology according to standardized laboratory procedures. Histology revealed a heterogeneous pattern of bone involvement. High cellularity of bone marrow, abundant presence of Gaucher cells (GCs) and high turnover were observed in a patient with a history of multiple bone complications, while minimal bone turnover and few GCs were detected in the mildest affected patient in this series. An intermediate picture with relatively low bone turnover and a substantial amount of Gaucher cells was demonstrated in the third, moderately affected patient. No gross abnormalities in three biochemical markers of bone turnover (osteocalcin, N-terminal propeptide of type 1 procollagen and type 1 collagen C-terminal telopeptide) were noted. Plastic embedding and subsequent Goldner and TRAP staining offered a unique possibility to study bone histological findings in GD. Our data show that bone manifestations in GD may vary both clinically as well as histologically and bone disease in GD will likely require a personalized approach.

Topics: Acid Phosphatase; Adult; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Bone and Bones; Bone Diseases; Gaucher Disease; Humans; Isoenzymes; Male; Middle Aged; Osteocalcin; Peptide Fragments; Procollagen; Tartrate-Resistant Acid Phosphatase

To evaluate the effects of the lercanidipine on bone healing (BH) and bone density (BD) in the tibiae of spontaneously hypertensive rats (SHR), using histometric and tartrate-resistant acid phosphatase (TRAP) expression analyses.. Wistar and SHR were assigned to one of the following groups: normotensive rats (NTR) (n = 15), untreated SHR (n = 15), and lercanidipine-treated SHR (n = 15). The latter group was treated daily with lercanidipine for 6 weeks. Two weeks after the beginning of drug administration, a critical-sized surgical defect was created in the right tibia of all groups, whereas the contralateral tibia remained without defect. The animals were killed 30 days after the creation of the bone defect.. There were no significant differences among the groups for BH, trabecular BD, and the number of TRAP+ cells in the newly formed cortical bone (P > 0.05). SHR presented significantly lower cortical BD and increased cortical levels of TRAP+ cells, when compared with NTR and lercanidipine-treated SHR (P < 0.05).. SHR presented a lower cortical BD and increased levels of TRAP+ cells. In addition, the treatment of SHR with lercanidipine during 6 weeks was able to revert the deleterious effects of hypertension on cortical BD and on the number of TRAP+ cells in the tibia of SHR.

Topics: Acid Phosphatase; Animals; Antihypertensive Agents; Biomarkers; Bone Density; Bone Diseases; Bone Regeneration; Calcium Channel Blockers; Dihydropyridines; Hypertension; Image Processing, Computer-Assisted; Isoenzymes; Male; Rats; Rats, Inbred SHR; Rats, Wistar; Tartrate-Resistant Acid Phosphatase; Tibia; Wound Healing

Tartrate-resistant acid phosphatase (TRACP) is an enzyme common to cells of the mononuclear phagocyte system and a clinically relevant biomarker for osteoclasts and inflammatory macrophages. The purpose was to assess applications and performance of six anti-TRACP monoclonal antibodies.. Mab9C5, 14G6, 162, 203, 220, and 89 were used as capture and detection antibodies in quantitative immunoassay, and for western blot (WB), immunoprecipitation, and immunohistochemistry of paraffin sections containing chronic inflammatory infiltrates. The clinical performance of mab14G6 for immunoassay of serum TRACP5b activity was compared to two commercial kit methods.. Mab9C5 is useful for WB and immunohistochemistry methods only. Mab14G6, 162, and 203 are useful for quantitative immunoassay and immunoprecipitation, however, mab203 causes inactivation of enzymatic activity. Mab220 and 89 are specific for TRACP5a and useful in all applications. Mab14G6 has similar clinical sensitivity and specificity as two commercial methods.. TRACP is an important marker in osteoimmunology. Specific antibodies with unique specificity for TRACP isoforms and defined applications will be valuable for clinical evaluation of bone metabolic, inflammatory and autoimmune diseases and will aid in basic research of TRACP biochemistry and biology.

Topics: Acid Phosphatase; Antibodies, Monoclonal; Biomarkers; Bone Diseases; Humans; Immunoassay; Isoenzymes; Sensitivity and Specificity; Tartrate-Resistant Acid Phosphatase

Thyrotoxicosis is more frequent in postmenopausal women than in the general population, effectively accelerating bone turnover. Interleukin-6 has been shown to be involved in the pathogenesis of bone disorders. Thus, the aim of the present study was to assess the role of IL-6 and its soluble receptor in the pathogenesis of thyrotoxicosis-related disturbances of bone turnover in oestrogen-deficient women.. The study was carried out in 40 subjects with toxic nodular goitre in three groups: Group 1 - 13 premenopausal females, mean age 36 ± 15 years (PremTx→PremEu); Group 2 - 12 postmenopausal females, mean age 66 ± 14 years (PostTx→PostEu); and Group 3 - 15 males, mean age 45 ± 21 years (MTx→MEu). Overt thyrotoxicosis and euthyreosis after treatment with thyrostatics were confirmed by thyrotropin, free thyroxine and free triiodothyronin concentrations. Serum levels of bone turnover markers: TRACP5b and osteocalcin as well as serum IL-6 and IL-6sR were determined using ELISA kits.. TRACP5b/osteocalcin quotient was significantly elevated in the PostTx females compared to the PremTx women (p < 0.02). There was a positive correlation between serum TRACP5b and osteocalcin in the studied patients (R = 0.45, p < 0.001). Levels of serum IL-6 values were significantly elevated in PostTx: 3.0 (2.14-6.40) and MTx: 2.24 (1.60-5.10), compared to PremTx females: 1.39 (0.96-2.14) (p < 0.01 and p < 0.05 respectively). There were significant positive correlations between IL-6 and IL-6sR concentrations (R = 0.22, p < 0.05) and between IL-6sR and TRACP5b serum levels (R = 0.23, p < 0.05).. The results of our study suggest that interleukin-6 plays a considerable role in the pathogenesis of thyrotoxicosis-related disturbances of bone turnover in oestrogen-deficient women.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Biomarkers; Bone and Bones; Bone Density; Bone Diseases; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-6; Isoenzymes; Male; Middle Aged; Osteocalcin; Osteoporosis, Postmenopausal; Receptors, Interleukin-6; Sex Factors; Tartrate-Resistant Acid Phosphatase; Thyrotoxicosis; Young Adult

Known biomarkers of Gaucher-disease activity are platelets, chitotriosidase, angiotensin-converting enzyme (ACE), tartrate-resistant acid phosphatase (TRAP) and ferritin. The aim of this study was to retrospectively evaluate the frequency of bone events (BE) and biomarker changes during two periods: diagnosis to first enzyme-replacement therapy (ERT) and the latter to the closing date.. BE of 62 treated patients, among the 73-patient cohort followed at Beaujon Hospital, Clichy, France, were described with Kaplan-Meier curves, and linear-mixed models were used to analyze their biomarker changes and the influence of several covariates (splenectomy, diagnosis year, genotype, age at diagnosis and sex).. BE occurred before (54 events in 21 patients), but also during, ERT (12 events in 10 patients), with respective frequencies (95% confidence interval) at 10 years of 22.4% (13.3 to 36.3) and 20.0% (10.2 to 36.9). Biomarker slope changes before and during ERT differed significantly for platelets (+190/mm3/year and 7,035/mm3/year, respectively; P < 0.0001) and ferritin (+4% and -14%; P < 0.0001). High ferritin levels and low platelet counts at ERT onset were significantly associated with BE during ERT (P = 0.019 and 0.039, respectively). Covariates significantly influenced biomarker changes (baseline and/or slope): splenectomy affected platelets (baseline and changes), TRAP changes and chitotriosidase changes; diagnosis date influenced ACE and TRAP baseline values; and genotype influenced chitotriosidase baseline and changes.. Platelet counts and ferritin levels and their slope changes at ERT onset seem to predict BE during treatment. Biomarker baseline values and changes are dependent on several covariables.

Topics: Acid Phosphatase; Adolescent; Adult; Biomarkers; Bone Diseases; Child; Child, Preschool; Cohort Studies; Disease Progression; Enzyme Replacement Therapy; Female; Ferritins; Fractures, Bone; Gaucher Disease; Glucosylceramidase; Hexosaminidases; Humans; Infant; Isoenzymes; Kaplan-Meier Estimate; Male; Middle Aged; Peptidyl-Dipeptidase A; Platelet Count; Predictive Value of Tests; Retrospective Studies; Tartrate-Resistant Acid Phosphatase; Young Adult

This study aimed to establish sex- and age-specific reference curves enabling the calculation of z-scores and to examine correlations between bone markers and anthropometric data.. Morning blood samples were obtained from 572 healthy children and adolescents (300 boys) aged 2 months to 18 yr. Height, weight, and pubertal stage were recorded. Serum osteocalcin (OC), bone-specific alkaline phosphatase (BALP), type-1 collagen degradation markers [carboxyterminal telopeptide region of type I collagen (ICTP), carboxyterminal telopeptide alpha1 chain of type I collagen (CTX)], and tartrate-resistant acid phosphatase (TRAP5b) were measured. Cross-sectional centile charts were created for the 3rd, 50th, and 97th centiles.. Apart from TRAP5b, all bone markers were nonnormally distributed, requiring logarithmic (BALP, OC, ICTP) or square root (CTX) transformation. Back-transformed centile curves for age and sex are presented for practical use. All bone markers varied with age and pubertal stage (P < 0.001). Significant correlations were found between sd score (SDS) for bone formation markers BALP and OC (r = 0.13; P = 0.004), SDS for collagen degradation markers ICTP and CTX (r = 0.14; P = 0.002), and SDS for the phosphatases (r = 0.34, P < 0.001). Height and weight SDS correlated weakly with some bone marker SDS, particularly with lnBALP SDS (r = 0.20 and 0.24, respectively; both P < 0.001).. This study provides reference curves for OC, BALP, CTX, ICTP, and TRAP5b in healthy children. Taller and heavier individuals for age had greater bone marker concentrations, likely reflecting greater growth velocity. SDS for markers of bone formation, collagen degradation, and phosphatases were each independently correlated, suggesting they derive from the same biological processes. The possibility of calculating SDS will facilitate monitoring of antiresorptive therapy or disease progression in children with metabolic bone disease.

Topics: Acid Phosphatase; Adolescent; Age Factors; Alkaline Phosphatase; Anthropometry; Biomarkers; Bone and Bones; Bone Diseases; Chemistry, Clinical; Child; Child, Preschool; Collagen Type I; Endocrinology; Female; Humans; Infant; Isoenzymes; Male; Osteocalcin; Peptide Fragments; Peptides; Procollagen; Reference Values; Sex Factors; Tartrate-Resistant Acid Phosphatase

Interleukin-6 (IL-6) has been shown to be involved in the pathogenesis of several bone diseases characterized by a negative balance between bone resorption and formation. The aim of the study was to estimate serum markers of bone turnover: osteoclast-derived tartrate-resistant acid phosphatase form 5a (TRACP 5b) reflecting resorption, and osteocalcin as a marker of bone formation in IL-6 knock-out mice to assess the role of IL-6 in the pathogenesis of thyrotoxicosis-related disturbances of bone metabolism. The study was performed on forty, 14-15 weeks old, female mice: C57BL/6J (wild-type; WT) and C57BL/6J (IL6-/-Kopf) (IL-6 knock-out; IL6KO). The mice were randomly divided into 4 groups with 10 mice in each one: 1. WT mice in thyrotoxicosis (WT-thx), 2. WT controls (WT-ctrl), 3. IL6KO mice with thyrotoxicosis (IL6KO-thx), and 4. IL6KO controls. Experimental model of hyperthyroidism was induced by intraperitoneal injection of levothyroxine at a dose of 1 microg/g, daily over 21 days. The serum levels of TRACP 5b and osteocalcin were determined by ELISA. Serum concentration of TRACP 5b (median and interquartile ranges) were significantly increased in both groups of mice with thyrotoxicosis: WT [28.2(18.8-41.6) U/l] and IL6KO [26.4(23.0-31.2) U/l] as compared to the respective controls. Osteocalcin serum levels in IL6KO-thx mice [111.9(103.1-175.6) ng/ml] were significantly elevated in comparison to WT-thx animals [46.1(32.5-58.9) ng/ml]. In summary, the results of the present study suggest that IL-6 plays a crucial role in thyrotoxicosis-related disturbances of bone turnover in mice, determining the imbalance between bone resorption and bone formation caused by excess of thyroid hormones predominantly by inhibition of bone formation.

Topics: Acid Phosphatase; Animals; Biomarkers; Bone Density; Bone Diseases; Densitometry; Female; Genotype; Interleukin-6; Isoenzymes; Mice; Mice, Inbred C57BL; Mice, Knockout; Osteocalcin; Tartrate-Resistant Acid Phosphatase; Thyroid Gland; Thyrotoxicosis

The derangements in bone metabolism in patients with chronic renal failure (CRF) are summarized as uremic bone disease (UBD). In this study, we planned to determine the serum prolidase to compare it with the other biochemical markers. This study was performed on 44 patients (19 females, 25 males, mean age = 56.8 +/- 15.6 years) with endstage renal disease (ESRD). The patients were divided into three groups according to serum bone alkaline phosphatase (bAP) levels. The patients whose bAP was > or =77 U/L were accepted as having high-turnover UBD (n=18), the patients whose bAP was < or =50 U/L were accepted as having low-turnover UBD (n=14), and the patients whose bAP levels were between these two values were accepted as having bone disease with normal turnover (n=12). The serum prolidase levels did not increase in patients with ESRD. There were no significant differences between the serum prolidase levels of patients according to types of the UBD (p > 0.05). Kidney is the most prolidase-rich tissue of the human body. The serum prolidase activity is low in all patients with ESRD, irrespective of the type of UBD. Therefore, we concluded that prolidase had no value in the diagnosis of UBD.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Biomarkers; Bone Diseases; Dipeptidases; Female; Humans; Isoenzymes; Kidney Failure, Chronic; Male; Middle Aged; Statistics as Topic; Statistics, Nonparametric; 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

A case of giant cell granuloma (GCG) that occurred in the right temporal bone is reported. The lesion showed histologic features identical to GCG. The multinuclear giant cells (MGCs) in the lesion showed strong reactivity with CD68, but patchy staining for myeloid/histiocyte antigen, alpha-1-antitrypsin, alpha-1-antichymotrypsine, and lysozyme. Activity of tartrate-resistant acid phosphatase was also consistently detected in the MGCs. Some of the mononuclear cells of the lesion exhibited similar immunocytochemical and histochemical reactivity as the MGCs. Ki-67 staining, however, was only detected in the mononuclear cells. The MGCs isolated from the lesion presented characteristic morphology of osteoclasts and possessed the ability to excavate bone in vitro. Thus, the MGCs in GCG appeared to express both macrophage- and osteoclast-associated phenotypes. The mononuclear cells were the major proliferative elements in the lesion and a subpopulation of these cells may represent precursors of the MGCs.

Topics: Acid Phosphatase; Adult; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Bone Diseases; Culture Techniques; Follow-Up Studies; Granuloma, Giant Cell; Humans; Immunohistochemistry; Isoenzymes; Male; Tartrate-Resistant Acid Phosphatase; Temporal Bone

To assess how two different serum markers of bone resorption may reflect changes in bone turnover, we compared age- and sex-related changes in serum C-terminal telopeptide of type I collagen (betaCTx) and tartrate-resistant acid phosphatase activity (TRAP) in 136 healthy men and 184 normal women. Serum levels of the two markers were also assessed in several groups of patients of both sexes presenting with the most common metabolic and endocrine bone diseases: established osteoporosis (n = 77), primary hyperparathyroidism (n = 44), glucocorticoid excess (n = 17), chronic renal failure (n = 39), active Paget's disease of bone (n = 5), humoral hypercalcemia of malignancy (n = 3), osteomalacia (n = 3), hyperthyroidism (n = 10), post-surgical hypoparathyroidism (n = 10), acromegaly (active disease, n = 8) and Cushing's syndrome (n = 10). In men the regression of betaCTx with age showed an initial decrease in bone resorption followed by an increase thereafter, starting from the sixth decade of life. No age-related change in serum TRAP activity was observed. In women, by contrast, a slight but significant linear correlation of both serum betaCTx and TRAP with age (r = 0.223, p<0.003 and r = 0.333, p<0.0001, respectively) was found, the two markers being positively correlated (r = 0.238, p<0.002). In each class of patients the mean Z-scores of betaCTx were significantly higher than those of TRAP activity. Moreover, compared with normal subjects, serum betaCTx seems to be characterized by a superior sensitivity relative to TRAP measurement, at least in the disorders studied.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Aging; Biomarkers; Bone Diseases; Bone Diseases, Endocrine; Bone Diseases, Metabolic; Bone Resorption; Collagen; Collagen Type I; Female; Humans; Isoenzymes; Male; Middle Aged; Peptides; Sex Characteristics; Tartrate-Resistant Acid Phosphatase

To investigate the cellular mechanism of bone destruction in collagen-induced arthritis (CIA).. After induction of CIA in DA rats, a histologic study of the advanced arthritic lesion was carried out on whole, decalcified joints from the hindpaws of affected animals. To conclusively identify osteoclasts, joint tissue sections were stained for tartrate-resistant acid phosphatase (TRAP) enzyme activity, and calcitonin receptors (CTR) were identified using a specific rabbit polyclonal antibody. The expression of messenger RNA (mRNA) for the osteoclast differentiation factor (also known as receptor activator of nuclear factor kappaB ligand [RANKL]) was investigated using in situ hybridization with a specific riboprobe.. TRAP-positive and CTR-positive multinucleated cells were invariably detected in arthritic lesions that were characterized by bone destruction. Osteoclasts were identified at the pannus-bone and pannus-subchondral bone junctions of arthritic joints, where they formed erosive pits in the bone. TRAP-positive multinucleated cells were detected within synovium and at the bone erosive front; however, CTR-positive multinucleated cells were present only at sites adjacent to bone. RANKL mRNA was highly expressed in the synovial cell infiltrate in arthritic joints, as well as by osteoclasts at sites of bone erosion.. Focal bone erosion in CIA is attributed to cells expressing definitive features of osteoclasts, including CTR. The expression of RANKL by cells within inflamed synovium suggests a mechanism for osteoclast differentiation and activation at sites of bone erosion. Inhibitors of RANKL may represent a novel approach to treatment of bone loss in rheumatoid arthritis.

Topics: Acid Phosphatase; Animals; Arthritis, Rheumatoid; Biomarkers; Bone Diseases; Carrier Proteins; Collagen; Disease Models, Animal; Female; Histocytochemistry; In Situ Hybridization; Isoenzymes; Membrane Glycoproteins; RANK Ligand; Rats; Receptors, Calcitonin; Tartrate-Resistant Acid Phosphatase

The major elements of bone pathology in Gaucher disease are a failure of osteoclast and osteoblast function, resulting in osteopenia and also osteonecrosis. T lymphocytes have recently been found to be involved in the regulation of osteoblast/osteoclast activity in vitro. In the present report the peripheral blood T major lymphocyte subsets were investigated in a group of genotyped type 1 Gaucher disease patients. A total of 31 patients were studied: 21 non-splenectomized (5 N370S homozygotes) and 10 splenectomized (of whom 1 was a N370S homozygote). The results show that non-splenectomized patients present a decrease in absolute numbers of peripheral blood T lymphocytes, specially the CD4+ T subset. However, when patients were analyzed with respect to the presence of bone disease, the number of CD8+ T lymphocytes was found to be statistically significantly lower in patients presenting bone involvement. Furthermore, lower numbers of CD8+ T lymphocytes were significantly correlated with higher levels of plasma tartrate resistant acid phosphatase (TRAP) activity, a putative marker of osteoclast cell activity. These in vivo findings are in agreement with the results reached in vitro by others. They provide an additional marker of disease severity in Gaucher disease. In the group of genotyped Gaucher disease patients, the majority of the N370S homozygous patients presented a clinically milder phenotype, including the absence of bone involvement, confirming earlier reports predicting that a number of these patients may remain undiagnosed. Collectively the homozygosity for the N370S mutation and normal T cell numbers may provide additional markers for the clinical heterogeneity of Gaucher disease.

Topics: Acid Phosphatase; Adolescent; Adult; Bone Diseases; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Child; Female; Gaucher Disease; Genotype; Glucosylceramidase; Humans; Isoenzymes; Lymphocyte Count; Male; Middle Aged; Recombinant Proteins; Splenectomy; T-Lymphocytes; Tartrate-Resistant Acid Phosphatase

A tibial lengthening scheme in the mouse was used to study the molecular and cellular events regulating tissue regeneration during distraction osteogenesis. Here, we report on the surgical technique and frame design and describe the histochemical and molecular aspects of distraction during different phases of treatment. A total of 26 mice were used in this study. The treatment protocol was divided into a latency period of 7 days, a phase of active distraction that lasted 10 days with a distraction rate of 0.42 mm/day, and a maturation phase of 9 days. During latency, the distraction site resembled a stabilized fracture callus on both a histochemical and a molecular level. During active distraction, the gap was characterized by a central fibrous interzone bordered by primary matrix fronts, regenerate bone aligned with the distraction force, parallel columns of vascular sinusoids, and a medullary cavity. Alkaline phosphatase activity was detected in the endosteal and periosteal surfaces of the bone ends. Tartrate resistant acid phosphatase staining revealed that osteoclasts remodeled the bone regenerate as it formed. Collagen type I was expressed in the periosteum and the primary matrix front during distraction, whereas collagen type-II transcripts were localized to discrete regions on the periosteal surfaces, immediately adjacent to the osteotomy ends. Collagen type-II transcripts were not detected in the fibrous interzone. During the maturation phase, cells within the fibrous interzone expressed collagen type I and exhibited abundant alkaline phosphatase activity, suggesting that they had begun to terminally differentiate. Collectively, these data demonstrate the utility of a mouse model to study the molecular and cellular bases for the regeneration and remodeling of tissue.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Bone Diseases; Bone Regeneration; Bony Callus; Collagen; Disease Models, Animal; External Fixators; Mice; Osteogenesis, Distraction; Radiography

We have characterized four monoclonal antibodies (mAbs) to the purple ("tartrate-resistant," band 5) acid phosphatase of the human osteoclast (TRAP) and used these to develop a specific serum immunoassay. All four mAbs are of high affinity (Ka = 1-5 x 10(8) L/mol) with a very fast Kassoc (0.2-2.0 x 10(5) L mol-1 s-1) and a moderate Kdissoc (1-3 x 10(-3) s). Two of the mAbs were selected to develop a time-resolved fluorescence immunoassay to measure serum concentrations of TRAP. The mean serum immunoreactive TRAP in a group of healthy premenopausal women and men was 3.7 +/- 1.8 micrograms/L (mean +/- SD) and 3.5 +/- 1.6 micrograms/L, respectively. Significantly higher concentrations of TRAP were found in postmenopausal women (6.3 +/- 2.3 micrograms/L) and in eight patients with Gaucher disease (19.3 +/- 4.7 micrograms/L). Further studies are required to investigate the value of serum TRAP as a marker of bone resorption.

Topics: Acid Phosphatase; Adolescent; Adult; Antibodies, Monoclonal; Antibody Affinity; Biomarkers; Bone Diseases; Bone Resorption; Female; Fluoroimmunoassay; Gaucher Disease; Humans; Isoenzymes; Male; Middle Aged; Postmenopause; Premenopause; Recombinant Proteins; Sensitivity and Specificity; Tartrate-Resistant Acid Phosphatase

Gaucher disease is the most frequent lysosomal storage disease and the most prevalent genetic disease among the Ashkenazi Jews (q approximately 0.047). The disease results from inherited defects of acid beta-glucosidase and the accumulation of the substrate, glucosylceramide, in cells of monocyte/macrophage origin. The therapeutic response to macrophage-targeted (alpha-mannosyl-terminated) alglucerase (Ceredase, at 60 to 15 IU/kg every 2 weeks) was analyzed in 33 patients (age range, 2 to 63 years; 15 splenectomized) with extensive Gaucher disease over periods of 6 to 24 months. The efficacy of several different doses and dosage reductions was evaluated. In patients with anemia (n = 30) and/or thrombocytopenia (n = 19), hemoglobin levels and platelet counts increased by 0% to 178% and 15% to 155%, respectively, within 3 to 12 months. In patients with splenomegaly (n = 17) and/or hepatomegaly (n = 28), liver and spleen volumes decreased in 6 months from 7% to 64% and 8% to 84% by 12 months, respectively. Hematologic and visceral improvements were noted at any doses between 60 and 15 IU/kg every 2 weeks. Furthermore, these positive initial therapeutic responses were persistent throughout therapy, with doses reduced by 50%. Pulmonary Gaucher disease did not improve clinically in 3 patients. Unrelated cirrhotic (n = 2), cholestatic (n = 1), or renal disease (n = 1) did not influence the rate of patient improvement. Two of five patients who developed serum antibodies against alglucerase during the first 6 to 12 months of therapy had mild antibody reactions. This study shows similar regression of clinical Gaucher disease manifestations with enzyme therapy, using doses between 30 and 60 IU/kg every 2 weeks. Therapeutic efficacy was not diminished after 50% to 75% dose reductions or in the presence of anti-enzyme antibodies.

Topics: Acid Phosphatase; Adolescent; Adult; Anemia; Bone Diseases; Child; Child, Preschool; Gaucher Disease; Glucosylceramidase; Hepatomegaly; Humans; Kidney Diseases; Liver Diseases; Lung Diseases; Middle Aged; Peptidyl-Dipeptidase A; Splenectomy; Splenomegaly; Thrombocytopenia

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Bone Diseases; Bone Neoplasms; Humans; Male; Middle Aged; Prostatic Hyperplasia; Prostatic Neoplasms; Radioimmunoassay

Acid phosphatase activity was determined in serum, cultured fibroblasts, and peripheral blood lymphocytes of six splenectomized adult patients with non-neuropathic Gaucher disease in two Canadian families. Elevated levels of serum acid phosphatase activity (520-711% of normal) were found in four patients who also developed orthopedic complications associated with Gaucher disease, including intermittent bone pain, arthritis, collapse of femoral head, and pathological fractures. Serum acid phosphatase activity in two patients who do not have bone involvement were found to be within the normal range. Contrary to the serum enzyme, acid phosphatase activity in lymphocytes and cultured fibroblasts of all of the patients was within the normal range. Deficient glucocerebrosidase (7.5-15.5% of normal) and acid beta-glucosidase (13.8-27.8% of normal) activities were noted in all probands. Similarly, normal levels of fibroblast and lymphocyte acid phosphatase activity were found in Gaucher heterozygotes whose glucocerebrosidase activity was about 50% of normal. Acid polyacrylamide gel electrophoresis and acid phosphatase activity staining of the patients' sera showed that the elevated acid phosphatase is isozyme type 5 osteoclastic origin. The apparent Michaelis constant, Km, of fibroblast glucocerebrosidase for the natural substrate was 0.6 +/- 0.1 mM for controls and 0.6 +/- 0.2 mM for the patients. These data suggest that the assay of serum acid phosphatase activity for the presumptive diagnosis of Gaucher disease is not completely reliable and that the elevated level of serum acid phosphatase in Gaucher disease is most likely a secondary phenomenon which may be indicative of bone involvement in some patients with this disorder. It also demonstrates the clinical heterogeneity of type 1 Gaucher disease, even among full sibs of the same heterozygous parents.

Topics: Acid Phosphatase; Adult; Bone Diseases; Electrophoresis, Polyacrylamide Gel; Female; Fibroblasts; Gaucher Disease; Glucosidases; Glucosylceramidase; Heterozygote; Humans; Kinetics; Lymphocytes; Male; Middle Aged

Topics: Acid Phosphatase; Adult; Bone Diseases; Child; Child, Preschool; Colorimetry; Electrophoresis, Polyacrylamide Gel; Gaucher Disease; Humans; Immunoenzyme Techniques; Infant; Middle Aged; Splenectomy; Tartrates

Topics: Acid Phosphatase; Bone Diseases; Electrophoresis, Polyacrylamide Gel; Humans; Isoenzymes; Male; Prostatic Neoplasms; Reference Values

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Diseases; Bone Neoplasms; Diagnosis, Differential; gamma-Glutamyltransferase; Humans; Male; Neoplasm Metastasis; Neoplasm Staging; Prostatic Neoplasms

The diagnostic value of bone pain in 227 consecutive patients with known primary tumor was investigated and bone scans were obtained. Eighty-two of 130 patients with bone pain had metastases with positive scans. In contrast, 80 of 97 patients without pain did not have metastases and the scans were negative; 13, however, did have metastases and positive scans, and in 10 of these the lesions were osteoblastic. Osteoblastic metastases may not produce pain. In a group of 70 patients with bone pain of unknown origin or elevated phosphatase levels, bone scans were also obtained and evaluated. Only one had metastatic disease, 40 were negative, and 29 had positive scans due to benign disease. It is concluded that in the assessment of malignancies, bone pain is a good indication for bone scintigraphy, except in those patients with osteoblastic lesions. However, when malignant disease has not yet been established, bone pain is not a reliable indication for scanning and radiographic examination is the initial examination of choice.

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Diseases; Bone Neoplasms; Diagnostic Errors; Female; Humans; Pain; Radionuclide Imaging

The case histories of three patients, a man and two boys, with disappearing bone disease are reported. The clinical, roentgenographic, and histopathological features are described in detail. Histologically, in the early stages of the disease, the vanishing bone is replaced by numerous wide engorged capillaries. Eventually the bone is replaced by dense fibrous tissue. All three patients were treated by radiotherapy. Histochemical studies performed in one case revealed strong acid phosphatase and leucine aminopeptidase activities in perivascular mononuclear cells (possibly pericytes), suggesting that these cells took part in the bone resorption.

Topics: Acid Phosphatase; Adolescent; Adult; Bone Diseases; Child, Preschool; Humans; Leucyl Aminopeptidase; Male; Osteolysis, Essential; Radiography

In a preliminary study, the effects of a biodegradable collagen gel on the healing of osseous defects were examined. Histologic and biochemical observations made on the seventh day after placement revealed that the collagen gel is well tolerated by the recipient and might be an effective stimulator of the formation of reparative bone. However, between the seventh and fourteenth days after placement, the deposition of reparative osseous tissues at the site of implant was significantly retarded. The possible implication of these findings is discussed.

Topics: Acetylglucosaminidase; Acid Phosphatase; Alkaline Phosphatase; Animals; Bone and Bones; Bone Diseases; Collagen; Connective Tissue; Fibroblasts; Gels; Glucuronidase; Guinea Pigs; Male; Wound Healing

The bones of adult rats became progressively osteopenic 1 to 5 weeks following jejunoileal bypass or resection. These changes were accompanied by increased levels of metaphyseal enzyme activities as well as by loss of histochemically identifiable osteoid. Osteoid tissue and the ability to mineralize skeletal collagen were recovered more rapidly and fully in the resection group than in the bypass group. Metaphyseal alkaline phosphatase concentrations increased in both groups coincident with the elevated lysosomal enzymes levels, and the skeletons showed a calcium deficit (low Ca/HOPr ratio) within the first 3 weeks. In resected rats the osteopenia and bone blood chemistry were consistent with hyperparathyroidism secondary to impared Ca absorption. In bypassed rats the results suggest that the osteopenia might be related to the release of a "resorptive factor" from the excluded intestinal segment.

Topics: Acid Phosphatase; Animals; Bone and Bones; Bone Diseases; Calcium; Female; Glucuronidase; Glycosaminoglycans; Hydroxyproline; Intestine, Small; L-Lactate Dehydrogenase; Magnesium; Malate Dehydrogenase; Methods; Phosphorus; Postoperative Complications; Rats; Sulfatases

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Diseases; Calcium; Humans; Phosphates

Topics: Acid Phosphatase; Adult; Alkaline Phosphatase; Bone Diseases; Buffers; Citrates; Enzyme Activation; Humans; Hydrogen-Ion Concentration; Indicators and Reagents; Intestines; Liver; Magnesium; Male; Methods; Phenolphthaleins; Prostate; Quaternary Ammonium Compounds; Spectrophotometry

Topics: Acid Phosphatase; Alkaline Phosphatase; Amylases; Biliary Tract Diseases; Bone Diseases; Clinical Enzyme Tests; Creatine Kinase; Enzymes; Humans; Isoenzymes; Liver Diseases; Male; Muscular Diseases; Myocardial Infarction; Nervous System Diseases; Organ Specificity; Oxidoreductases; Pancreatic Diseases; Prostatic Diseases; Pulmonary Embolism; Transaminases

Topics: Acid Phosphatase; Bone Diseases; Bone Marrow; Humans; Hyperparathyroidism; Kidney; Kidney Diseases; Liver; Liver Diseases; Male; Neoplasms; Parathyroid Glands; Prostate; Prostatic Neoplasms; Spleen

Topics: Acid Phosphatase; Aminopropionitrile; Animals; Bone Diseases; Brain; Cathepsins; Chorea; Citrates; Collagen; Connective Tissue; Glycoside Hydrolases; Granuloma; Lathyrism; Male; Nitriles; Polyvinyls; Rats; Sodium Chloride

Topics: Acid Phosphatase; Bone Diseases; Bone Neoplasms; Carcinoma; Female; Gaucher Disease; Humans; Hyperparathyroidism; Male; Neoplasm Metastasis; Prostate; Prostatic Neoplasms; Pulmonary Embolism

Topics: Acid Phosphatase; Adult; Aged; Blood Platelet Disorders; Bone Diseases; Bone Neoplasms; Female; Gaucher Disease; Humans; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms; Pulmonary Embolism

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Diseases; Fibroblasts; Humans

Topics: Acid Phosphatase; Adult; Alkaline Phosphatase; Bone Diseases; Bone Neoplasms; Breast Neoplasms; Child; Female; Humans; Infant, Newborn; Lactation; Male; Methods; Pregnancy; Prostatic Neoplasms

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Bone Diseases; Calcium; Mice; Mutation; Phosphorus

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Bone Diseases; Male; Swine; Swine Diseases; Vitamin A

Topics: Acid Phosphatase; Adult; Alkaline Phosphatase; Bone Diseases; Child; Child, Preschool; Female; Humans; Infant; Male; Middle Aged; Osteopetrosis

Topics: Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Bone Diseases; Calcium; Female; Humans; Male; Mandibular Neoplasms; Maxillary Neoplasms; Middle Aged; Phosphorus

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

Topics: Abnormalities, Drug-Induced; Acid Phosphatase; Alkaline Phosphatase; Animals; Bone Diseases; Chick Embryo; Chickens; Collagen; Embryology; Histocytochemistry; Hydroxyproline; Insulin; Poultry; Proteins; Research; Tibia; Toxicology

Topics: 5'-Nucleotidase; Acid Phosphatase; Alkaline Phosphatase; Biliary Tract; Biliary Tract Diseases; Bone Diseases; Disease; DNA; Leucyl Aminopeptidase; Liver Diseases; Pancreas; Pancreatic Diseases; Peptide Hydrolases; Phosphoric Monoester Hydrolases; Protein Tyrosine Phosphatases; RNA; Trees