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L Malaval

Publications and source records attributed to L Malaval.

At least 37 records · Page 2Linked to original sources
PubMed1994

Cellular expression of bone-related proteins during in vitro osteogenesis in rat bone marrow stromal cell cultures.

Rat bone marrow stromal cells comprise a heterogeneous mixture of cell lineages including osteoblastic cells. When grown in the presence of ascorbic acid, beta-glycerophosphate and 10(-8) M dexamethasone, osteoprogenitor cells within the population divide and differentiate to form bone nodules (Maniatopoulos et al., 1988, Cell Tissue Res., 254:317-330; Aubin et al., 1990, J. Bone Miner. Res., 5:S81) providing a useful model to investigate temporal and spatial changes in expression of osteoblastic markers. Immunocytochemistry was combined with Northern blotting, enzymatic assay, and radioimmunoassay to analyze the expression of bone-related proteins during the growth and differentiation sequence. By mRNA levels, protein production and/or enzymatic activity, expression of osteocalcin, bone sialoprotein, and alkaline phosphatase increased concomitantly with the development of bone nodules, while osteopontin mRNA levels decreased and those of SPARC/osteonectin did not change significantly. In older cultures with mineralizing nodules, mRNA levels for alkaline phosphatase and bone sialoprotein, but not osteocalcin, declined. Immunolabeling revealed that cells in early cultures stained poorly for SPARC/osteonectin and strongly for thrombospondin. Later, SPARC/osteonectin staining increased in most cells, while thrombospondin staining could be seen in both matrix and in cells, but with marked intercellular variability in intensity. At all time points studied, osteoblasts within bone nodules stained homogeneously for thrombospondin and alkaline phosphatase, and with marked heterogeneity of intensity amongst cells for SPARC/osteonectin and osteocalcin. Labelling with RCC455.4, a monoclonal antibody raised against rat calvaria cells which intensely labels osteoblasts and osteocytes (Turksen et al., 1992, J. Histochem. Cytochem., 40:1339-1352), co-localized with osteocalcin. Alkaline phosphatase activity and the amount of osteocalcin determined by both radioimmunoassay and immunolabelling decreased in very late cultures, a time corresponding to appearance of fully mineralized nodules. These studies indicate that the bone marrow stromal cell system is a useful model to study the temporal and spatial expression of bone-related proteins during osteogenesis and formation, mineralization, and maturation of bone nodules. Further, immunolabelling at the individual cell and single bone nodule level allowed discrimination of marked variability of expression of osteoblast markers during the differentiation sequence.

Alkaline Phosphatase↗
PubMed1994

Simultaneous detection of multiple bone-related mRNAs and protein expression during osteoblast differentiation: polymerase chain reaction and immunocytochemical studies at the single cell level.

Messenger RNA expression analyzed by in situ hybridization and Northern analysis and protein expression analyzed biochemically or immunocytochemically have been used to study the developmental expression of various osteoblast (OB)-associated molecules. These approaches have shown that over a time course of OB differentiation in vivo and in vitro, the expression of macromolecules associated with OB cells changes. However, ambiguities in data from different approaches and in populations representative of cells at different developmental stages are extant. To begin to discriminate differentiation stages with more precision and to address intercellular heterogeneity, fetal rat calvaria cells were grown at low densities under conditions in which bone nodules form and mineralize and colonies were classified morphologically as fibroblastic or osteoblastic (early, intermediate, or mature). Whole discrete colonies and single cells from individual colonies were analyzed molecularly by a random amplification poly(A)-polymerase chain reaction (PCR) and for protein expression by immunocytochemistry; we analyzed the expression of known bone-related macromolecules (collagen type I, alkaline phosphatase, osteopontin, bone sialoprotein, and osteocalcin). Both PCR and immunocytochemistry revealed that different colony types were reproducibly distinguishable in their expression of either general (collagen type I) or bone-associated (alkaline phosphatase, osteopontin, bone sialoprotein, and osteocalcin) macromolecules, such that fibroblastic colonies were distinguishable from osteoblastic colonies and the latter could be subdivided into less mature or more mature osteoblastic colonies. While some aspects of the temporal differentiation sequence defined earlier were confirmed, several additional features were evident from these single cell-single colony studies. First, different repertoires of OB-associated markers were expressed in different cells, suggesting variation in the switch-on of the OB differentiation program and heterogeneity in the OB phenotype. Second, among colonies classified as fibroblastic on the basis of morphology heterogeneity was also evident and there were some cells expressing features consistent with their being osteoprogenitor cells. Our data support the hypothesis that individual fibroblastic and osteoblastic cells are heterogeneous in expression of marker molecules. We also conclude that individual cells and colonies analyzed by poly(A)-PCR will be useful in lieu of mass populations to extend investigation of stages in the progression of OB differentiation.

Alkaline Phosphatase↗
PubMed1994

Transient expression of SPARC in the dorsal axis of early Xenopus embryos: correlation with calcium-dependent adhesion and electrical coupling.

Our comprehension of the molecular mechanisms underlying embryogenesis has been greatly enhanced by the identification and characterization of associated extracellular matrix macromolecules. Using Xenopus laevis as a model, we investigated the expression and distribution of SPARC (Secreted Protein, Acidic, Rich in Cysteine; also called osteonectin and BM-40) during early embryonic development. SPARC has been found to be enriched in tissues undergoing rapid morphological development, differentiation, and remodeling. In Xenopus, SPARC transcripts are first expressed by primordial cells which give rise to the first embryonic tissues, the notochord and somites. SPARC RNA levels remained high throughout the rapid morphological development and differentiation phase of these tissues, and then rapidly decreased. Of particular interest, SPARC protein began to accumulate within the intersomitic clefts at the onset of trunk myotome contraction. The intersomitic enrichment of SPARC remained high as long as the myotomes remained electrically coupled, principally by gap junctions. As myotomes became innervated, SPARC expression decreased dramatically within the somites. SPARC was also found to be enriched within other tissues, such as the neural tube and epidermis. In addition, the selective spatial-temporal enrichment of SPARC suggests it makes important calcium-dependent contributions to early morphological development.

Animals↗
PubMed1992

Localization of platelet osteonectin at the internal face of the alpha-granule membranes in platelets and megakaryocytes.

Osteonectin is a 32-Kd phosphoglycoprotein originally described in bone but also found in platelets. Platelet and bone osteonectin are different both structurally and immunologically. We have previously shown that platelet osteonectin, by binding to thrombospondin, is involved in the secretion-dependent phase of the platelet aggregation process. In this study, we used antiosteonectin antibodies in combination with immunogold labeling to investigate by electron microscopy the fine localization of osteonectin within normal and gray platelets. Using both a polyclonal and monoclonal antibody ON3, osteonectin was specifically located at the internal face of alpha-granule membranes within normal platelets. Osteonectin was not distributed within all alpha-granules, probably because of its low platelet content. In addition, using immunofluorescence, osteonectin could also be detected in immature and mature megakaryocytes with a granular pattern of staining, suggesting that osteonectin is synthesized by megakaryocytes. Using platelets from two patients with gray platelet syndrome, osteonectin was absent within all abnormal small alpha-granules, but was detected in some rare normal-sized alpha-granules. In separate double-label studies, thrombospondin and von Willebrand factor did not colocalize with osteonectin in resting platelets. However, osteonectin was located at the inner face of the alpha-granules, as it is for alpha-granule membrane protein GMP-140 and glycoprotein IIb-IIIa. These results, taken together with the fact that monoclonal antibodies to osteonectin bind only to the surface of activated platelets, suggest that platelet osteonectin is redistributed to the cell surface during fusion of alpha-granule membranes with the plasma membrane.

Blood Platelets↗
PubMed1992

Immunological screening of SPARC/Osteonectin in nonmineralized tissues.

SPARC/Osteonectin is a major bone-related protein that is also present in nonmineralized tissues and in platelets. As compared to bone SPARC/Osteonectin, SPARC/Osteonectin from platelets presents a slightly lower electrophoretic mobility in SDS-PAGE and a 100-fold decreased affinity for a unique monoclonal antibody, Mab2 (Malaval et al. 1991). To check the tissular diversity of SPARC/Osteonectin, protein extracts from bovine bone, nonmineralized tissues, and platelets were screened by immunoblotting and immunoradiometric assay, with Mab2 and three other monoclonal antibodies recognizing distinct epitopes. The SPARC/Osteonectin secreted by a human osteosarcoma cell line (MG63) was also tested. In all the nonmineralized tissues tested (gut, bone marrow, tendon, mesentery, artera, lens, skin, liver, and cornea), SPARC/Osteonectin presents the same immunoreactivity and electrophoretic mobility as in bone. The heavier molecular weight and Mab2-negative form present in platelets seems to be unique to this cell type. Osteosarcoma cell extracts and conditioned media give the same results as bone extracts, indicating that the low molecular weight and Mab2-positive form of SPARC/Osteonectin present in most tissues does not result from proteolytic cleavage in the matrix, but is secreted as such. Bone and platelet SPARC/Osteonectin present different patterns of sensitivity to glycosidases, suggestive of a difference in N-glycosylation. However, these treatments do not affect the decreased affinity of Mab2 for platelet SPARC/Osteonectin, which is not likely to be related to difference in N-glycosylation.

Animals↗
PubMed1991

Intertissular variations in osteonectin: a monoclonal antibody directed to bone osteonectin shows reduced affinity for platelet osteonectin.

Osteonectin, a major noncollagenous protein of bone, is also synthesized and secreted by various non-mineralized tissues and by platelets. To establish whether there are structural specificities of osteonectin according to its tissular origin, we raised 12 monoclonal antibodies against bovine bone osteonectin and screened them for their ability to recognize bone and platelet osteonectin. When hybridoma culture media were radioimmunoassayed all MAbs showed the same titer for [125I]human platelet osteonectin and for [125I]bovine bone osteonectin, except MAb 2, which poorly bound platelet osteonectin. Immunoprecipitation and immunoblotting experiments were performed on human bone protein extracts and on material secreted by human platelets upon thrombin stimulation; in these experiments MAb 2 recognized human bone osteonectin and only faintly human platelet osteonectin. A "sandwich" immunoradiometric assay was devised in which osteonectin bound to a solid phase by a first MAb was recognized by a 125I-labeled second MAb. In this assay MAb 2, used as a tracer, showed a 100-fold lower affinity for purified human platelet osteonectin than for purified human bone osteonectin. These results suggest the existence of structural variations in osteonectin obtained from bone and platelets. Whether these variations result from differences in sequence, post-translational processing, or postsecretional fate remains to be established.

Amino Acid Sequence↗
PubMed1991

Osteonectin is an alpha-granule component involved with thrombospondin in platelet aggregation.

We previously showed that thrombospondin, a major alpha-granule glycoprotein of human platelets, forms a specific complex with osteonectin, a phosphoglycoprotein originally described in bone that is also present in human platelets. The storage organelles and the function of osteonectin in platelets are still unknown. In this study, using electron microscopy in combination with immunogold staining, the major storage organelle for platelet-secreted proteins, the alpha-granules. Furthermore, osteonectin was qualitatively and quantitatively assessed by studying normal platelets and the platelets from a patient with gray platelet syndrome. Gray platelet syndrome is a rare congenital bleeding disorder characterized by a selective deficiency in morphologically recognizable platelet alpha-granules and in the alpha-granule secretory proteins. Binding of an iodinated antiosteonectin monoclonal antibody to gray platelet proteins transferred to nitrocellulose from SDS-polyacrylamide gels showed no band corresponding to osteonectin compared to control platelets. Using a polyclonal antiosteonectin antibody-based radioimmunoassay, gray platelets contained 0.2 +/- 0.03 ng osteonectin per 10(6) platelets, which is only 20% of the normal platelet content of osteonectin (0.93 +/- 0.16 ng per 10(6) platelets). Study of the localization of osteonectin to the surface of human platelets demonstrated that a radioiodinated antiosteonectin polyclonal antibody bound specifically to thrombin-stimulated platelets but not to resting platelets. Binding was concentration-dependent, saturable (1710 +/- 453 binding sites per platelet, Kd = 1 microM), and inhibited by an excess of cold antiosteonectin polyclonal antibody. No binding was observed on the surface of thrombin-stimulated gray platelets. To gain further insights into the role of osteonectin released from activated platelets, the effect of an antiosteonectin polyclonal antibody was tested on the aggregation of washed platelets. F(ab')2 fragments from the antiosteonectin polyclonal antibody inhibited in a dose-dependent manner the aggregation of collagen-stimulated, washed human platelets without affecting collagen-induced platelet serotonin release. To characterize the mechanism through which antiosteonectin F(ab')2 fragments inhibit platelet aggregation, the expression of endogenous thrombospondin (TSP) on the surface of thrombin-activated platelets was studied using 125I-labeled anti-TSP monoclonal antibody P10. The endogenous surface expression of TSP to thrombin-stimulated platelets was significantly inhibited in the presence of antiosteonectin F(ab')2 fragments (6286 +/- 2065 molecules of P10 per platelet) compared to 11,230 +/- 766 molecules of P10 per platelet in the presence of nonimmune F(ab')2 fragments.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1991

Epitope mapping of two monoclonal antibodies to the central portion of human osteonectin.

In this study preliminary characterization of two monoclonal antibodies against osteonectin was undertaken. One monoclonal originally raised against bovine bone osteonectin cross reacts with human bone and platelet osteonectin. The other monoclonal antibody has been reported to react with osteonectin derived from human bone and bovine bone but not to the same extent with that from platelets. Initial mapping of the antigenic determinants for both monoclonals was done by testing their ability to bind to the expressed forms of osteonectin in two overlapping SaOS-2 lambda gt11 osteonectin cDNA clones. One clone contains a 0.54 kb insert and is comprised of 50 nucleotides of 5' noncoding and a coding segment for a 17 amino acid signal peptide and 146 amino acids of the N-terminal region of the mature protein. The other clone has a 1.9 kb insert, and includes amino acid no. 18 to the C-terminus of the molecule (amino acid no. 286), a single termination codon, and 1115 nucleotides of 3' noncoding sequence. Both monoclonals recognized expressed osteonectin from the two lambda gt11 SaOS-2 cDNA clones. These results localize the epitope to a region between amino acids 18-146 of osteonectin.

Amino Acid Sequence↗
PubMed1990

Circulating levels of osteonectin in normal subjects and patients with thrombocytopenia.

In order to clarify the relative contributions of activated platelets and other sources to circulating osteonectin, the amounts of osteonectin present in serum and in plasma prepared without significant platelet activation were compared to platelet count in normal subjects and patients with various degrees of thrombocytopenia. Serum osteonectin showed a logarithmic positive correlation with platelet count (r = 0.87, P less than 0.0001, n = 52). Osteonectin concentration was significantly lower in plasma than in matched sera in all subjects sampled, and not significantly different in plasma of thrombocytopenic and normal subjects. These results confirm the major contribution of platelets to serum osteonectin. The positive zero intercept of the plot osteonectin vs. platelet count (19 +/- 2.45 ng/ml, mean +/- SD, P less than 0.0001, n = 52) and the presence of significant amounts of osteonectin in plasma, document the existence of a basic level of circulating osteonectin, independent of platelet activation, and to which the relative contribution of bone remains to be assessed.

Adult↗
PubMed1988

Complex formation of human thrombospondin with osteonectin.

Human thrombospondin, a 450-kDa glycoprotein isolated from platelets and endothelial cells, specifically interacts with osteonectin, a protein of 30 kDa isolated from bovine bones and human platelets. Using ELISA, purified osteonectin binds to solid-phase-adsorbed thrombospondin with a dissociation constant (Kd) of 0.7 nM. Binding of thrombospondin to solid-phase-adsorbed osteonectin was also observed (Kd = 0.86 nM). The interaction of thrombospondin with solid-phase-adsorbed osteonectin was significantly decreased (81% inhibition) when using an excess of fluid-phase osteonectin. Thrombospondin-osteonectin complex formation was calcium-dependent as shown by a 50-80% inhibition in the presence of EDTA. None of the proteins known to interact with thrombospondin (fibrinogen, fibronectin, collagen, plasminogen) had a significant inhibitory effect on thrombospondin-osteonectin complex formation. This selective interaction was confirmed by affinity chromatography. Iodinated osteonectin, previously incubated with purified thrombospondin, specifically bound to an anti-thrombospondin monoclonal antibody (P10) linked to protein-A--Sepharose 4B. Elution of the anti-thrombospondin antibody from protein A allowed the recovery of the thrombospondin-osteonectin complex in the eluate, as judged by SDS/polyacrylamide gel electrophoresis and autoradiography. Blotting of purified thrombospondin to osteonectin adsorbed onto nitrocellulose further confirmed complex formation. In addition, when released from thrombin-stimulated platelets, thrombospondin and osteonectin bound to anti-thrombospondin IgG-coated plates indicating that osteonectin was complexed to thrombospondin once the platelet-release reaction has occurred.

Animals↗
PubMed1987

Radioimmunoassay for osteonectin. Concentrations in bone, nonmineralized tissues, and blood.

We describe a double antibody radioimmunoassay for the bone protein osteonectin using a polyclonal antibody raised against bovine fetal bone osteonectin. This assay, which cross-reacts with human osteonectin, was used to explore the tissue distribution of the protein. Osteonectin was detected in extracts of nonmineralized tissues from bovine fetuses, with concentrations ranging from 10 ng/100 micrograms of proteins in the lens to about 80 ng/100 micrograms in collagen-rich tissues (e.g., tendon), which represents respectively from 0.01% to 0.5% of the concentrations found in bone extracts. Osteonectin is thus a widespread component of extracellular matrix, although its concentration is minute in tissues other than bone and dentin. Adult human serum contains 200 ng/ml of osteonectin and values obtained in plasma prepared without platelet activation are about one-third of those in matched sera. This platelet-independent fraction might be used as a marker for bone metabolism.

Amino Acids↗
PubMed1986

[Osteocalcin (or bone gla-protein), a new biological marker for studying bone pathology].

Osteocalcin, also called bone gla-protein, is a bone matrix protein synthetized specifically by osteoblasts. It circulates in blood where it can be assayed by the radioimmune method. We measured osteocalcin serum levels in 169 adult controls and 161 patients with different disseminated or localized bone diseases. The normal concentration of 6.2 +/- 0.2 ng/ml increases significantly with age. Serum osteocalcin levels are considerably increased in renal osteodystrophy (114 +/- 23 ng/ml) and to a lesser degree in primary hyperparathyroidism (15.9 +/- 2.8 ng/ml) and Paget's disease (11.4 +/- 0.9 ng/ml), all diseases characterized by increased bone turnover. High levels are also encountered in osteomalacia (9.7 +/- 0.9 ng/ml). Conversely, serum osteocalcin levels are significantly decreased in patients under long-term corticosteroid therapy (4.3 +/- 0.5 ng/ml); they remain normal in patients with bone myeloma and bone metastases under treatment. Finally, osteocalcin is normal in patients with osteoporosis, but its level reflects that of bone turnover as evaluated by iliac bone biopsy. The circulating osteocalcin therefore is the first specific and sensitive marker for bone turnover. Serum osteocalcin measurements make it possible to evaluate the osteoblastic bone formation without biopsy and should provide information on the effectiveness of drugs acting on the bone-forming process.

Adrenal Cortex Hormones↗
PubMed1986

Serum bone GLA-protein in growth hormone deficient children.

Serum bone GLA-protein (BGP), a sensitive and specific marker of bone formation, was measured in 54 normal children and in 50 children with growth disorders. In normal children, the pattern of variations of serum BGP with age was similar to the pattern of variations of the growth velocity. Mean serum BGP was very high during the first year of life (25.3 +/- 8.5 ng/ml), decreased to 14.8 +/- 2.2 ng/ml from 2 to 6 years, increased to 18.4 +/- 4.1 ng/ml from 7 to 10 years and to 18.8 +/- 6.5 ng/ml from 11 to 14 years. After puberty, mean sBGP decreased to 12.9 +/- 5.4 ng/ml from 15 to 18 years and to 6.5 +/- 1.4 ng/ml in young adults. In 32 patients with untreated growth hormone (GH) deficiency, mean sBGP was markedly lower than in age matched controls (6.8 +/- 4.4 ng/ml vs. 17.5 +/- 4.9 ng/ml, p less than .001). In 19 patients with GH deficiency who were undergoing treatment with human GH, sBGP was higher than in untreated patients (20.5 +/- 9.3 ng/ml vs. 6.8 +/- 4.4 ng/ml, p less than .001) and was not different from controls. Repeated measurements performed in 14 GH-deficient patients under chronic GH therapy showed that serum BGP: (1) increased in most patients during treatment (p less than .005); (2) was correlated with the duration of treatment (p less than .001); (3) decreased to pretreatment values after discontinuing therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Serum bone GLA-protein is not a sensitive marker of bone turnover in Paget's disease of bone.

Serum bone Gla-protein (sBGP) was measured in 32 patients with untreated Paget's disease of bone. Despite clinical and biological symptoms of active disease in all patients, sBGP was normal in 13/32 patients (41%). There was a striking discrepancy between the moderate increase of sBGP above normal values (11.4 +/- 4.5 vs 6.0 +/- 2.1 ng/ml) and the marked increase of both serum alkaline phosphatase (sAP) and urinary hydroxyproline (uOHP). sBGP was weakly correlated with sAP (r = 0.50, p less than 0.01), uOHP (r = 0.48, p less than 0.01) and with the extension of the disease (r = 0.48, p less than 0.01). We conclude that sBGP is not a sensitive marker of bone turnover in patients with Paget's disease of bone, and should be interpreted with caution in this condition.

Alkaline Phosphatase↗
PubMed1986

Serum bone gamma carboxyglutamic acid-containing protein in primary hyperparathyroidism and in malignant hypercalcemia. Comparison with bone histomorphometry.

Serum bone gamma-carboxyglutamic acid-containing (Gla) protein (sBGP), a sensitive and specific marker of bone turnover, was measured in 25 patients with primary hyperparathyroidism and in 24 patients with bone metastases with or without hypercalcemia. Despite similar levels of hypercalcemia, sBGP was increased in primary hyperparathyroidism (14.2 +/- 9.6 ng/ml, P less than 0.001), was decreased in malignant hypercalcemia (3.1 +/- 2.8 ng/ml, P less than 0.001), and was normal in patients with bone metastases without hypercalcemia (6.6 +/- 2.7 ng/ml). In primary hyperparathyroidism, sBGP was correlated with serum immuno-reactive parathyroid hormone (r = 0.90), calcium (r = 0.73), and with the adenoma weight (r = 0.79). After parathyroidectomy, sBGP slowly returned to normal values within 2-6 mo, suggesting that sBGP reflects increased bone turnover rather than a direct effect of parathyroid hormone on BGP synthesis at the cell level. An iliac crest biopsy was performed in 11 patients with primary hyperparathyroidism and in 9 cancer patients in a noninvaded area. sBGP was significantly correlated with all parameters reflecting bone formation but not with bone resorption. Patients with bone metastases were analyzed according to the presence or the absence of hypercalcemia. In contrast to normocalcemic patients who had normal sBGP, hypercalcemic patients had decreased sBGP (P less than 0.001) and a lower bone formation at the cellular level (P less than 0.05). Thus, biochemical and histological data suggest that an unknown humoral factor might be responsible for this uncoupling between increased resorption and decreased formation. This uncoupling, rather than local release of calcium by the metastatic process, might be responsible for hypercalcemia in patients with bone metastases.

Adenocarcinoma↗
PubMed1986

Serum bone Gla protein: a marker of bone turnover in hyperthyroidism.

Serum bone Gla protein (BGP) concentrations were measured in 24 hyperthyroid patients before and after treatment. Before treatment, the mean concentration was higher [11.8 +/- 3.4 ( +/- SD) ng/ml] in the patient group than in a group of 12 age-matched normal subjects (6.1 +/- 1.7 ng/ml; P less than 0.001); 16 of the 24 patients had a value above the normal range. Serum BGP concentrations in the patients correlated significantly with serum T3 (r = 0.65; P less than 0.001) and T4 concentrations (r = 0.56; P less than 0.01). Other biochemical markers of bone metabolism (serum alkaline phosphatase, serum and urinary calcium, and urinary hydroxyproline) did not correlate with circulating thyroid hormone levels. Serum BGP also was measured after the patients had become euthyroid; 23 measurements were made on 16 patients at various times after the start of treatment. All values were normal after 16 weeks; before this period, most of the values were still above the normal range despite normal plasma thyroid hormone concentrations in all patients. These results suggest that BGP is a sensitive marker of bone metabolism alterations during hyperthyroidism.

Adult↗
PubMed1986

Serum bone Gla-protein in renal osteodystrophy: comparison with bone histomorphometry.

Serum bone Gla-protein (S-BGP) and other serum biochemical parameters, including alkaline phosphatase (S-AP) and immunoreactive PTH (S-iPTH), were measured in 42 patients undergoing chronic hemodialysis. Each patient also had a tetracycline-labeled transiliac bone biopsy, allowing correlations between the biochemical and trabecular bone histomorphometric parameters, S-BGP was markedly increased [64.0 +/- 74.8 (+/- SD) vs. 6.2 +/- 2.2 ng/ml in normal subjects] significantly correlated with S-AP (r = 0.53) and S-iPTH (r = 0.55) levels. S-BGP was significantly higher in the 14 patients with high turnover renal osteodystrophy (HT-ROD; S-BGP, 138.5 +/- 90.8 ng/ml) than in the 28 patients with low turnover (LT-ROD; S-BGP, 26.8 +/- 14.8 ng/ml). S-BGP was significantly correlated with the cellular parameters of bone resorption and formation (r = 0.57-0.69) and with the dynamic parameters of bone formation (r = 0.62-0.82). The extent of stainable bone aluminum was significantly negatively correlated with S-BGP (r = -0.51) and serum iPTH (r = -0.33), but not with S-AP. S-BGP measurement allowed better discrimination between LT-ROD and HT-ROD groups than did S-AP measurement. However, in the patients with LT-ROD, S-BGP did not discriminate between patients with or without osteomalacia. We conclude that S-BGP is a valuable marker for evaluating bone remodeling and, more specifically, the bone formation rate at the tissue level in hemodialyzed patients.

Adolescent↗