acid-phosphatase and Hypercalcemia

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

The aim of this paper is to summarize some of our quantitative descriptive and experimental studies, to discuss them in view of the literature data, and to present a synthesis of the topic. The results of stereological analysis of some tissue components of the rat thyroid gland have been compared with the results of topological studies on the parafollicular cells of various mammalian species. Localization of the parafollicular cells in the central regions of the thyroid gland lobes, where the follicular cell activity seems to be greater than in the periphery of the lobes, has led to the hypothesis that the parafollicular cells regulate (stimulate and/or suppress) the activity of the follicular cells. Long-term application and antithyroid drugs to mice and rats has shown that excessive concentrations of thyrotropin provoke hyperplasia of both the follicular cells and the intrathyroid mast cells and, transiently, of the parafollicular cells. This and some of the literature data are congruent with the hypothesis that the parafollicular and mast cells also stimulate the follicular cells by their paracrine secretions. Long-term application of antithyroid drugs to mice and rats has shown that excessive concentrations of cular cells but also probably stimulation of the follicular cells, as judged by the stereological measurements. The biological meaning of the spatial integration of follicular and parafollicular cells seems to be a functional coordination of both epithelial cell lines, supported by intrathyroid mast cells.

Topics: Acid Phosphatase; Animals; Antithyroid Agents; Autoradiography; Histocytochemistry; Humans; Hypercalcemia; Hypocalcemia; Mast Cells; Spectrophotometry; Thyroid Gland

Topics: Acid Phosphatase; Adult; Alkaline Phosphatase; Calcitonin; Calcium; Calcium Metabolism Disorders; Child; Clinical Enzyme Tests; Cyclic AMP; Female; Humans; Hydroxyproline; Hypercalcemia; Hypocalcemia; Magnesium; Male; Parathyroid Hormone; Phosphates; Steroids; Vitamin D

Topics: Acid Phosphatase; Adenocarcinoma; Aniline Compounds; Bone Neoplasms; Cyclophosphamide; Evaluation Studies as Topic; Fluorouracil; Humans; Hypercalcemia; Hypophysectomy; Male; Mechlorethamine; Neoplasm Metastasis; Plicamycin; Prostatic Neoplasms

Lanthanum carbonate (LC) is a non-calcium-containing phosphate binder and shows a comparable effect with other phosphate binders on hyperphosphatemia in dialysis patients. LC also contributes to a reduced oral calcium load compared with calcium carbonate (CaC) treatment. However, no crossover studies which compare the influence on serum calcium level between treatments with LC and CaC in hemodialysis (HD) patients have been carried out.. After washout for 2 weeks, 50 patients on HD were randomized (1 : 1) to receive LC or CaC for 3 months. Thereafter, patients underwent a second 2-week washout period and were switched to the alternative binder for the next 3 months. Mineral and bone metabolism markers were measured with the changes of vitamin D doses.. The serum phosphate level showed a similar decrease from baseline to 3 months in both groups. During the study periods, hypercalcemia was observed only in patients taking CaC. The dose of vitamin D analogue was increased more frequently in the patients of the LC group compared with LC group. The iPTH level showed a significant decrease in the CaC group, but not in the LC group. Serum levels of BAP, TRAP5b, and ALP were significantly elevated in the LC group, whereas the FGF-23 level showed a significant decrease.. LC effectively reduced the serum phosphate level (like CaC) and allowed the vitamin D analogue dosage to be increased without hypercalcemia in HD patients. LC is one of the useful phosphate binders without hypercalcemia. (UMIN-CTR registration number: UMIN000002331).

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Analysis of Variance; Calcium; Calcium Carbonate; Chelating Agents; Chi-Square Distribution; Cross-Over Studies; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Hypercalcemia; Hyperphosphatemia; Isoenzymes; Lanthanum; Male; Middle Aged; Parathyroid Hormone; Phosphorus; Renal Dialysis; Renal Insufficiency, Chronic; Tartrate-Resistant Acid Phosphatase; Vitamin D

Our human observational study showed that elevated arginine vasopressin levels by heavy exercise, not catecholamines, were associated with elevated serum tartrate-resistant acid phosphatase 5b (TRACP-5b). The increase in serum calcium was positively associated with percent changes of TRACP-5b, implying the involvement of bone resorption in the pathogenesis of exercise-induced hypercalcemia.. It remains unclear whether enhanced bone resorption explains exercise-induced hypercalcemia. An experimental study demonstrated that arginine vasopressin (AVP) stimulated osteoclast activity.. We conducted a prospective observational study, enrolling 65 trained healthy male officers of the Japan Self-Defense Forces (34 and 31 in waves 1 and 2, respectively). Before and after a 5-h heavy exercise, we collected laboratory data including bone markers, symptoms, and ionized calcium (iCa; wave 2 only). As blood calcium levels change after exercise, we estimated calcium (corrected calcium) levels immediately after the exercise using the correlation between blood calcium and time from the end of exercise in another cohort.. Body weight decreased by 6.9% after the exercise. Corrected post-exercise serum total calcium (tCa) and iCa levels were significantly higher than pre-exercise levels, and 18% of participants showed hypercalcemia defined as corrected tCa >10.4 mg/dL or iCa >1.30 mmol/L. Serum tartrate-resistant acid phosphatase 5b (TRACP-5b), plasma three fractions of catecholamines, and AVP elevated significantly (median 14.3 pg/mL), while procollagen type 1 N-terminal propeptide and whole parathyroid hormone showed significant decreases. Corrected tCa increase showed a non-linear positive association with percent changes of TRACP-5b (%ΔTRACP-5b) even after adjustment for confounders. In addition, %ΔTRACP-5b was not associated with catecholamines, but with post-exercise AVP levels after adjustment for pre-exercise TRACP-5b. Symptoms of nausea or vomiting (observed in 20%) were positively associated with corrected post-exercise iCa after adjustment for post-exercise blood pH.. AVP elevation may explain bone resorption and the following hypercalcemia in the setting of heavy exercise.

Topics: Acid Phosphatase; Biomarkers; Bone Resorption; Humans; Hypercalcemia; Isoenzymes; Male; Tartrate-Resistant Acid Phosphatase; Vasopressins

p38 mitogen-activated protein kinase (MAPK) acts downstream in the signaling pathway that includes receptor activator of NF-κB (RANK), a powerful inducer of osteoclast formation and activation. We investigated the role of p38 MAPK in parathyroid hormone related protein (PTHrP)-induced osteoclastogenesis in vitro and PTHrP-induced bone resorption in vivo. The ability of FR167653 to inhibit osteoclast formation was evaluated by counting the number of tartrate-resistant acid phosphatase positive multinucleated cells (TRAP-positive MNCs) in in vitro osteoclastgenesis assays. Its mechanisms were evaluated by detecting the expression level of c-Fos and nuclear factor of activated T cells c1 (NFATc1) in bone marrow macrophages (BMMs) stimulated with sRANKL and M-CSF, and by detecting the expression level of osteoprotegerin (OPG) and RANKL in bone marrow stromal cells stimulated with PTHrP in the presence of FR167653. The function of FR167653 on bone resorption was assessed by measuring the bone resorption area radiographically and by counting osteoclast number per unit bone tissue area in calvaria in a mouse model of bone resorption by injecting PTHrP subcutaneously onto calvaria. Whole blood ionized calcium levels were also recorded. FR167653 inhibited PTHrP-induced osteoclast formation and PTHrP-induced c-Fos and NFATc1 expression in bone marrow macrophages, but not the expression levels of RANKL and OPG in primary bone marrow stromal cells treated by PTHrP. Furthermore, bone resorption area and osteoclast number in vivo were significantly decreased by the treatment of FR167653. Systemic hypercalcemia was also partially inhibited. Inhibition of p38 MAPK by FR167653 blocks PTHrP-induced osteoclastogenesis in vitro and PTHrP-induced bone resorption in vivo, suggesting that the p38 MAPK signaling pathway plays a fundamental role in PTHrP-induced osteoclastic bone resorption.

Topics: Acid Phosphatase; Animals; Bone Resorption; Calcium; Cell Count; Cells, Cultured; Humans; Hypercalcemia; Isoenzymes; Male; Mice; NFATC Transcription Factors; Osteoclasts; Osteogenesis; Osteoprotegerin; p38 Mitogen-Activated Protein Kinases; Parathyroid Hormone-Related Protein; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-fos; Pyrazoles; Pyridines; RANK Ligand; Tartrate-Resistant Acid Phosphatase

It is well established that calcitonin is a potent inhibitor of bone resorption; however, a physiological role for calcitonin acting through its cognate receptor, the calcitonin receptor (CTR), has not been identified. Data from previous genetically modified animal models have recognized a possible role for calcitonin and the CTR in controlling bone formation; however, interpretation of these data are complicated, in part because of their mixed genetic background. Therefore, to elucidate the physiological role of the CTR in calcium and bone metabolism, we generated a viable global CTR knockout (KO) mouse model using the Cre/loxP system, in which the CTR is globally deleted by >94% but <100%. Global CTRKOs displayed normal serum ultrafiltrable calcium levels and a mild increase in bone formation in males, showing that the CTR plays a modest physiological role in the regulation of bone and calcium homeostasis in the basal state in mice. Furthermore, the peak in serum total calcium after calcitriol [1,25(OH)(2)D(3)]-induced hypercalcemia was substantially greater in global CTRKOs compared with controls. These data provide strong evidence for a biological role of the CTR in regulating calcium homeostasis in states of calcium stress.

Topics: Acid Phosphatase; Actins; Animals; Calcitonin; Calcitriol; Calcium; Female; Femur; Gene Deletion; Gene Targeting; Hypercalcemia; Integrases; Isoenzymes; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Osteoclasts; Phenotype; Receptors, Calcitonin; Tartrate-Resistant Acid Phosphatase

To evaluate bone and calcium-phosphorus metabolism, bone tissue density (BTD) in smokers and non-smokers with chronic obstructive pulmonary disease (COPD).. The study included 120 patients with COPD; smokers (n=68), smokers in the past (n=8) and non-smokers (n=44). Control 80 healthy subjects were matched by age and sex. Bone metabolism was estimated by concentration of osteocalcin (OC), markers of bone resorption (TRAP, betaCrossLaps-betaCL).. Smoking aggravates disturbance of calcium metabolism in COPD leading to hypocalcaemia and hypercalciuria. In smokers with COPD bone remodeling dysfunction is caused by suppression of osteogenesis and enhancement of resorption, in non-smokers--intensification of both resorption and osteogenesis. The analysis of correlations has shown that there is a close correlation between the level of TRAP, bone mineral density scores and indices of pack-years (r = -075, p < 0.01; r = -0.6, p < 0.01, respectively). Anamnesis of smoking has a positive correlation with TRAP (r = 0.85, p < 0.001) and a negative correlation with bone density (r = -0.8, p < 0.01) and OC (r = -0.55, p < 0.01).. Duration of smoking (total pack-years) is an additional marker of osteopenic syndrome in COPD. This is confirmed by close correlation of this parameter with bone density and markers of bone resorption.

Topics: Acid Phosphatase; Aged; Biomarkers; Bone and Bones; Bone Density; Bone Diseases, Metabolic; Bone Resorption; Calcium; Female; Humans; Hypercalcemia; Male; Osteocalcin; Phosphorus; Pulmonary Disease, Chronic Obstructive; Smoking

IL-4 is an important immune cytokine that regulates bone homeostasis. We investigated the molecular mechanism of IL-4 action on bone-resorbing mature osteoclasts. Using a highly purified population of mature osteoclasts, we show that IL-4 dose-dependently inhibits receptor activator of NF-kappaB ligand (RANKL)-induced bone resorption by mature osteoclasts. We detected the existence of IL-4R mRNA in mature osteoclasts. IL-4 decreases TRAP expression without affecting multinuclearity of osteoclasts, and inhibits actin ring formation and migration of osteoclasts. Interestingly, IL-4 inhibition of bone resorption occurs through prevention of RANKL-induced nuclear translocation of p65 NF-kappaB subunit, and intracellular Ca(2+) changes. Moreover, IL-4 rapidly decreases RANKL-stimulated ionized Ca(2+) levels in the blood, and mature osteoclasts in IL-4 knockout mice are sensitive to RANKL action to induce bone resorption and hypercalcemia. Furthermore, IL-4 inhibits bone resorption and actin ring formation by human mature osteoclasts. Thus, we reveal that IL-4 acts directly on mature osteoclasts and inhibits bone resorption by inhibiting NF-kappaB and Ca(2+) signaling.

Topics: Acid Phosphatase; Actins; Active Transport, Cell Nucleus; Adult; Animals; Bone Resorption; Calcium Signaling; Carrier Proteins; Cell Differentiation; Cell Migration Inhibition; Glycoproteins; Humans; Hypercalcemia; Interleukin-4; Intracellular Fluid; Isoenzymes; Male; Membrane Glycoproteins; Mice; Mice, Inbred BALB C; Mice, Knockout; NF-kappa B; Osteoclasts; Osteoprotegerin; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Calcitonin; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; RNA, Messenger; Tartrate-Resistant Acid Phosphatase; Transcription Factor RelA

Parathyroid hormone (PTH) stimulates bone resorption as well as bone formation in vivo and in organ culture. The catabolic actions of PTH have been recognized in patients with hyperparathyroidism, or with acute infusion of the N-terminal 1-34 fragment of human PTH (hPTH1-34). Whereas the anabolic actions of daily injection with PTH have been well studied in both humans and mice, the catabolic actions of PTH on murine bone remain to be defined. To do this we sought to create a model with short-term, sustained hyperparathyroidism using osmotic infusion pumps. We treated 10-week-old female C57BL/J6 mice with continuous infusion of hPTH1-34 (8.1 pmol/0.25 microl per h, equivalent to 40 microg/kg per day) or vehicle for 2 weeks, using Alzet osmotic pumps. Bone mineral density (BMD), serum total calcium, hPTH1-34, mouse intact PTH (mPTH1-84), osteocalcin and mouse tartrate-resistant acid phosphatase (mTRAP) activity, and microarchitectural variables of the distal femur were measured. Separately, we compared the effects of intermittent daily injection of hPTH1-34 (40 microg/kg per day) with continuous infusion of hPTH1-34 on BMD and bone markers. Exogenous hPTH1-34 was detected only in the PTH-infused mice. Both intermittent and continuous treatment with hPTH1-34 markedly suppressed endogenous mPTH1-84, but only the latter induced hypercalcemia. Daily PTH injection significantly increased both serum osteocalcin and mTRAP, while continuous PTH infusion showed a strong trend to stimulate mTRAP, with a slight but non-significant increase in osteocalcin. There were significant differences in BMD at all sites between animals treated with the same daily dose of intermittent and continuous hPTH1-34. Micro-computed tomography (muCT) analysis of the distal femurs revealed that hPTH1-34 infusion significantly decreased trabecular connectivity density (P<0.05). Thus, the murine bone response to continuous PTH infusion was quite different from that seen with daily PTH injection. Short-term infusion of hPTH1-34 appears to be a good model to study the mechanisms underlying the catabolic action of PTH in mice.

Topics: Acid Phosphatase; Animals; Biomarkers; Bone and Bones; Bone Density; Dose-Response Relationship, Drug; Female; Femur; Humans; Hypercalcemia; Infusion Pumps, Implantable; Injections; Isoenzymes; Lumbar Vertebrae; Mice; Mice, Inbred C57BL; Osteocalcin; Random Allocation; Tartrate-Resistant Acid Phosphatase; Teriparatide; Tibia; Time Factors; Tomography, X-Ray Computed

Osteolysis and hypercalcemia are observed in 5-15%, and 10%, respectively, of malignant lymphoma patients during their clinical course. However, both osteolysis and hypercalcemia are uncommon at onset of the disease. We encountered a 24-year-old male non-Hodgkin's lymphoma patient who had multiple osteolytic lesion from the onset of the disease and repeated episodes of hypercalcemia during the clinical course. The patient died with refractory disease. We studied the expression of chemokines which might affect bone resorption using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. Increased expressions of MIP-1alpha, MIP-1beta and RANKL, which are osteoclast-activating factors, were observed in the RNA derived from the patient's lymphoma cells. The secretion of osteoclast-activating factors such as MIP-1alpha by the tumor cells (and/or bone marrow stromal cells) might be involved in the etiology of osteolysis and hypercalcemia in some malignant lymphoma cases.

Topics: Acid Phosphatase; Adult; Biopsy; Bone Marrow Cells; Bone Resorption; Carrier Proteins; Chemokine CCL3; Chemokine CCL4; Chemokines; Fatal Outcome; Humans; Hypercalcemia; Immunophenotyping; Isoenzymes; Low Back Pain; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Macrophage Inflammatory Proteins; Magnetic Resonance Imaging; Male; Membrane Glycoproteins; Osteoclasts; Osteolysis; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Reverse Transcriptase Polymerase Chain Reaction; Tartrate-Resistant Acid Phosphatase

In the present study, we used osteoprotegerin (OPG), which blocks osteoclastogenesis, to correct and thus explain the hypercalcemia that is seen during dietary Mg deficiency in the mouse. Control and Mg-deficient mice received injections for 12 days of either OPG or vehicle only. Serum Ca was similar in Mg-deficient mice treated with OPG and in control mice receiving OPG (9.2 +/- 0.3 mg/dl vs. 9.2 +/- 0.5). Both groups had significantly higher serum Ca than controls or Mg-deficient animals receiving vehicle alone. Surprisingly, Mg-depleted mice that received OPG in doses that inhibit osteoclastic bone resorption remained hypercalcemic. Because mature osteoclasts still present in the marrow might be hyperactive, we examined osteoclast morphology at the light microscopic and ultrastructural level. Light microscopic examination of trabecular bone showed few osteoclasts in OPG-treated mice. Ultrastructural examination revealed that osteoclasts in OPG-treated mice have decreased contact with the endosteal bone surface and absence of a ruffled border. Because the morphology of the existing pool of mature osteoclasts did not enhance resorption, another mechanism, such as increased intestinal absorption of Ca in Mg-deficient mice, likely contributes to the hypercalcemia observed during Mg deficiency.

Topics: Acid Phosphatase; Animals; Calcium; Female; Glycoproteins; Hypercalcemia; Isoenzymes; Magnesium Deficiency; Mice; Osteoclasts; Osteoprotegerin; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Tartrate-Resistant Acid Phosphatase

Using mouse osteoclast-like cells (OCs), we have shown that treatment with glucocorticoids (GCs) resulted in an increase in calcitonin (CT) binding by enhancing CT receptor (CTR) gene transcription. Additionally, treatment with GCs demonstrated increased sensitivity to CT. There is, however, scant information on the effects of GC or CTR regulation by GCs in human osteoclasts. In this study we examined CTR regulation by GCs and the effects of GCs and CT together in human OCs. OCs were prepared by treatment of peripheral blood mononuclear cells in vitro with soluble receptor activator of nuclear factor-kappaB ligand and macrophage colony-stimulating factor. Treatment of mature OCs with dexamethasone (Dex) resulted in a dose- and time-dependent increase in [(125)I]salmon CT (sCT) binding capacity. Treatment with Dex enhanced CTR messenger RNA (mRNA) expression, suggesting that CTR up-regulation is at least partly due to an increase in de novo CTR synthesis. Triamcinolone and prednisolone reproduced the Dex effect on [(125)I]sCT-specific binding and CTR mRNA expression, but 17beta-estradiol, progesterone, dehydroepiandrosterone, and aldosterone did not. A Scatchard plot analysis showed that Dex enhanced CTR number with a minimal change in the affinity to sCT. Autoradiographic studies using [(125)I]sCT showed that Dex enhanced the CTR density on individual multinuclear OCs. Up-regulation of [(125)I]sCT-specific binding and CTR mRNA expression was seen even in the presence of sCT, but the enhancement diminished subsequently at later times (36-48 h after sCT removal), which was consistent with our previous observation in mouse OCs. This suggests that GCs and CTs act on CTR expression differently, consistent with our previous work using mouse OCs, in which we found that GCs increased transcription of CTR gene expression, whereas CT reduced CTR mRNA stability. The results obtained in this study show that GC increased CTR expression and sensitivity to CT in cells of the human osteoclast lineage and provide the basis for understanding the beneficial effects of combination treatment with GCs and CTs in malignancy-associated hypercalcemia.

Topics: Acid Phosphatase; Autoradiography; Carrier Proteins; Cell Line; Cyclic AMP; Glucocorticoids; Humans; Hypercalcemia; Isoenzymes; Macrophage Colony-Stimulating Factor; Membrane Glycoproteins; Osteoclasts; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Calcitonin; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tartrate-Resistant Acid Phosphatase

This study evaluated the ability of bisphosphonate to prevent bone resorption induced by metastatic tumor cells.. Autopsy specimens of a bone metastasis from a woman with a primary squamous cell carcinoma of the tongue who developed multiple osteolytic lesions and hypercalcemia and was treated with pamidronate were studied histologically, histochemically, and ultrastructurally. In an animal experiment, cultured tumor cells (1 x 10(5)) obtained from a metastatic submandibular lymph node in the same patient were injected in the left ventricle of nude mice, and a resulting metastatic bone lesion was studied histologically and histochemically.. In the autopsy specimens, despite the presence of many resorption lacunae on bone surface, only a few small tartrate-resistant acid phosphatase (TRAPase)-positive cells were observed, and most of them were stained weakly and detached from the bone surface. In the animal experiment, 1 of 10 animals (10%) formed osteolytic bone metastasis, and many TRAPase-positive cells were observed histochemically.. Biphosphonate inhibits bone resorption induced by tumor, possibly by decreasing the number of osteoclasts and inhibiting their function.

Topics: Acid Phosphatase; Aged; Animals; Bone Neoplasms; Bone Resorption; Carcinoma, Squamous Cell; Diphosphonates; Female; Humans; Hypercalcemia; Isoenzymes; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Osteoclasts; Pamidronate; Spinal Neoplasms; Tartrate-Resistant Acid Phosphatase; Thoracic Vertebrae; Tongue Neoplasms; Tumor Cells, Cultured

Ascites sarcoma 180 (S180A) is a transplantable tumor maintained in ddY mice. In the tumor-bearing mice, the plasma Ca, Pi and acid phosphatase levels increased and the plasma alkaline phosphatase levels decreased. The elevation of plasma Pi levels is unusual in humoral hypercalcemia of malignancy (HHM). To characterize the pathogenesis of HHM in the animals, the biological activities in the serum-free conditioned media (CM) of S180A cell cultures were examined. The S180A CM stimulated bone resorption dose dependently and showed TGF-like, IL-1-like and mitogenic activity. Unlike parathyroid hormone (PTH), the factor(s) failed to stimulate cAMP production by either UMR 106-01 cells or neonatal mouse calvaria at concentrations that stimulate bone resorption. Also, the factor(s) stimulated proliferation of UMR 106-01 cells concomitant with a slight increase in intracellular calcium levels. These results indicate that S180A cells produce a factor(s) responsible for bone resorption which is apparently different from PTH-like activity.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Ascites; Bone Resorption; Calcium; Culture Media; Cyclic AMP; Hypercalcemia; Interleukin-1; Mice; Mitogens; Neoplasm Transplantation; Osteoclasts; Parathyroid Hormone; Phosphorus; Sarcoma 180; Transforming Growth Factors; Tumor Cells, Cultured

Cultures of a cell line derived from a murine mammary carcinoma that induces hypercalcemia were examined for soluble products that could induce osteoclasts to differentiate from murine bone marrow cells. The serum-free culture supernatant of this cell line stimulated growth of colonies from bone marrow cells that exhibited tartrate-resistant acid phosphatase (TRAPase) activity. These TRAPase-positive cells demonstrated essential features of osteoclasts when cultured with mineralized bone or dentin. The culture period required for colony development and the frequency of colony-forming cells indicated that relatively primitive marrow progenitors were stimulated by a tumor-derived factor(s) to form immature osteoclasts. Other colony-stimulating factors (CSFs), including granulocyte CSF, macrophage CSF, granulocyte-macrophage CSF and interleukin 3, were ruled out as the source of the activity produced by the tumor cells. The biological activity was successfully purified by gel filtration chromatography and reverse-phase HPLC. By SDS/PAGE, the activity was traced to a protein of approximately 17 kDa. Functional and biochemical studies of the purified factor suggest that it is distinct from any known CSF of myeloid cells. This protein appears to be a CSF for the osteoclast lineage, osteoclast CSF (O-CSF).

Topics: Acid Phosphatase; Adenocarcinoma; Animals; Chromatography, High Pressure Liquid; Colony-Stimulating Factors; Culture Media; Hypercalcemia; In Vitro Techniques; Mammary Neoplasms, Experimental; Mice; Molecular Weight; Osteoclasts; Tumor Cells, Cultured

Gallium nitrate is a clinically effective agent for the treatment of cancer related hypercalcemia. The mechanism of action of this agent was investigated following development of a quantitative in vivo bone resorption assay modified from the method of Glowacki. In a preliminary study, the time course of resorption of 50 mg subcutaneous implants of bone powder in growing rats was followed by chemical analysis of mineral (ash and Ca) contents, enzymatic and histochemical assay of tartrate resistant acid phosphatase (TRAP) activity, and image analysis of changes in particle size using von Kossa stained sections. Day 21 was chosen as a single time point for the comparison of the extent of resorption of gallium-containing and control bone particles. Resorption of bone particles containing 0.39 micrograms Ga/mg bone was significantly inhibited relative to control particles. Mineral content (6.7 vs. 3.6 mg), Ca content (1.72 vs. 1.37 mg), and the percentage of the field covered by bone particles (12 vs. 9%) were greater in the animals which received gallium-containing bone particles. Similarly, the number of osteoclast-like cells and the TRAP activity in the gallium-containing bone particle implants at 21 days were increased relative to controls. These data indicate that gallium incorporation into bone matrix confers resistance to resorption.

Topics: Acid Phosphatase; Animals; Bone and Bones; Bone Density; Bone Matrix; Bone Resorption; Calcium; Gallium; Hypercalcemia; Male; Osteoclasts; Particle Size; Rats; Rats, Inbred Strains; Tartrates

To evaluate the effects of calcitriol (1,25-dihydroxyvitamin D3) therapy for the bone disease induced by long-term treatment with anticonvulsants, we reviewed the medical records of 330 institutionalized oligophrenic children and young adults under 26 years of age to identify the 144 children who required anticonvulsant therapy. Of this latter group, 52 children were found to have serum alkaline phosphatase levels elevated more than 2 SDs above normal and were enrolled into this prospective three-year study. To achieve rapid resolution of the bone disease, we elected to use calcitriol at 0.25 to 0.75 micrograms/d. After 1195 patient-months of treatment, our data suggest that the dystrophic process was reversed in 42.3% of the cases, as judged by decreases in serum alkaline phosphatase levels at six months, 65.4% of cases at 12 months, and 83.3% of cases at 13 to 18 months. By 30 months of follow-up, all patients showed significant lowering of serum alkaline phosphatase levels. The improvements were slow and gradual. Twenty-six patients in the treatment series of 52 patients initially showed signs of rickets or osteomalacia on roentgenograms of the wrists. Of these 26 patients, 12 (46%) showed improvement on roentgenograms within 24 months of the beginning of treatment. With reference to complications, hypercalcemia (calcium level, greater than 11 mg/dL [2.74 mmol/L]) was encountered at the rate of one episode per 44 patient-months of treatment. Our results strongly suggest that calcitriol is effective in healing anticonvulsant-related osteomalacia among children and youths, with a low incidence of complications.

Topics: Acid Phosphatase; Adult; Anticonvulsants; Aspartate Aminotransferases; Calcitriol; Calcium; Child; Child, Preschool; Female; Humans; Hypercalcemia; Intellectual Disability; Male; Osteomalacia; Phosphates; Prospective Studies; Radiography; Rickets

Topics: Acid Phosphatase; Ammonium Chloride; Animals; Animals, Newborn; Bone and Bones; Fluorides; Hypercalcemia; Injections, Intraperitoneal; Mandible; Odontogenesis; Osteogenesis; Potassium Chloride; Proteins; Rats; Sodium Chloride; Tartrates; Tibia; Tooth; Vitamin D

Under observation were 66 (50.3%) of 130 patients with an ossific form of hyperparathyroidism. Fourty five patients showed the classical picture of Recklinghausen disease, and 21-only diffuse osteoporosis. The correct diagnosis would be established 4-5 years following the onset of the disease. During the period of most distinct manifestations pains in bones were noted in 93 per cent of cases. Two thirds of patients showed marked atonia and fatigue. Pathological fractures were multiple and were observed in 45 of 66 patients (totally 125 fractures). Great importance in establishing the diagnosis of the form of hyperparathroidism is attached to roentgenological investigation of all bones and biochemical assay of blood and urine.

Topics: Acid Phosphatase; Adult; Aged; Calcium; Female; Haptoglobins; Humans; Hypercalcemia; Male; Middle Aged; Osteitis Fibrosa Cystica; Osteoporosis; Phosphorus

Topics: Acid Phosphatase; Animals; Cholecalciferol; Cholinesterases; Chronic Disease; Esterases; Histocytochemistry; Hypercalcemia; Male; Rats; Thyroid Gland

Topics: Acid Phosphatase; Animals; Biopsy; Bone Resorption; Calcium; Calcium Radioisotopes; Culture Techniques; Frontal Bone; Hypercalcemia; Osteoclasts; Osteopetrosis; Parathyroid Hormone; Parietal Bone; Rats; Tibia; Tritium

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Blood Proteins; Bone and Bones; Calcium; Carcinoma; Creatinine; Glomerular Filtration Rate; Hypercalcemia; Hyperparathyroidism; Hypophosphatasia; Intestines; Kidney; Kidney Tubules; Liver; Magnesium; Male; Phosphorus; Rabbits; Thigh

Topics: Acid Phosphatase; Acute Disease; Adenosine Triphosphatases; Animals; Calcitonin; Chronic Disease; Esterases; Female; Histocytochemistry; Hypercalcemia; Hypocalcemia; Leucyl Aminopeptidase; Rats; Staining and Labeling; Thyroid Gland