Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Bone Resorption”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 829 records · Page 46Linked to original sources
PubMed1994

Diclofenac sodium inhibits bone resorption in postmenopausal women.

BACKGROUND: The results of experimental studies with animals indicated that prostaglandins stimulate bone resorption, that skeletal production of prostaglandin E2 is enhanced by ovariectomy and is diminished by 17 beta-estradiol, and that the nonsteroidal anti-inflammatory drug (NSAID) naproxyn prevents bone loss after ovariectomy. Studies were carried out to investigate the effects of the NSAID diclofenac sodium on bone and mineral metabolism in premenopausal women and to compare the effects of diclofenac sodium and conjugated estrogens on bone and mineral metabolism in postmenopausal women. PATIENTS AND METHODS: Ten healthy premenopausal women and 17 healthy postmenopausal women were studied while not being treated and again after 4 weeks of treatment with diclofenac sodium, 150 mg per day in divided doses (both groups), and conjugated estrogens, 0.625 mg per day (postmenopausal women). Cross-linked N-telopeptides of type I collagen were measured in the urine as an index of bone resorption. The postmenopausal women were separated into two groups, responders and nonresponders, based on their response to conjugated estrogens as assessed by linear discriminant analysis for groups. Conjugated estrogens lowered urinary N-telopeptides of type I collagen in responders, but not in nonresponders. RESULTS: Urinary cross-linked N-telopeptides were higher in the eight postmenopausal women responders than in the nine postmenopausal nonresponders or in the premenopausal women, and were not altered by diclofenac sodium in premenopausal women. In the eight postmenopausal women with higher rates of bone resorption, diclofenac sodium and conjugated estrogens significantly lowered both urinary calcium concentration and urinary cross-linked N-telopeptides. The effects of the two drugs were comparable. CONCLUSION: The preliminary results demonstrate that, at the dose used, diclofenac sodium is almost as effective as conjugated estrogens for decreasing bone loss in postmenopausal women. Further studies will be needed to determine whether diclofenac sodium can prevent postmenopausal bone loss.

Adult↗
PubMed1985

Diphenylhydantoin inhibits parathyroid hormone and prostaglandin E2-stimulated bone resorption in mouse calvaria without affecting cyclic AMP formation.

The effect of diphenylhydantoin (DPH) on mouse calvarial bone metabolism was studied in vitro. DPH caused a dose-dependent, reversible inhibition of PTH and PGE2-stimulated bone resorption at concentrations above 20-30 micrograms/ml without affecting cyclic AMP formation. The inhibition was observed already after 60 min and was accompanied by a reduced release of the lysosomal enzymes beta-glucuronidase and beta-N-acetylglucosaminidase. The calcium antagonist Verapamil had similar effects on bone resorption and lysosomal enzyme release and it is suggested that DPH influences bone resorption by interfering with calcium fluxes across osteoclastic cell membranes resulting in low intracellular calcium levels and reduced exocytotic processes.

Animals↗
PubMed1996

Leukotriene B4 stimulates osteoclastic bone resorption both in vitro and in vivo.

Upon activation, the enzyme 5-lipoxygenase converts arachidonic acid into principally three products, the peptidoleukotrienes, 5-hydroperoxyeicosatetraenoic acid (5-HETE) or the leukotriene B4. We have shown that the peptido-leukotrienes (known as LTC4, LTD4, or LTE4) and 5-HETE induce osteoclastic bone resorption and that receptors for LTD4 are present on isolated avian osteoclast-like cells. Here, we show the effects of the third metabolic product of the 5-lipoxygenase (5-LO) pathway of arachidonic acid metabolism, the leukotriene LTB4, on osteoclastic bone resorption both in vivo and in vitro. Because LTB4 production is increased in a number of inflammatory conditions, it may be an important contributor to the bone loss which occurs in these disorders. LTB4 increased osteoclastic bone resorption in vivo following local administration over the calvariae of normal mice and in vitro in organ cultures of neonatal mouse calvariae. When LTB4 was injected over the calvaria of mice, there was a significant increase in bone resorption, osteoclast numbers, and eroded surfaces. LTB4 also increased the formation of resorption lacunae by isolated neonatal rat osteoclasts. Greater potency was observed with LTB4 compared with the peptido-leukotriene LTD4. This is in contrast to prostaglandins of the E series, which are reported to inhibit isolated osteoclasts. Experiments using marrow cultures suggest that LTB4 stimulates bone resorption in part by enhancing the formation of osteoclasts.

Analysis of Variance↗
PubMed2002

Inhibitory effect of a Korean traditional medicine, Honghwain-Jahage (water extracts of Carthamus tinctorius L. seed and Hominis placenta) on interleukin-1-mediated bone resorption.

A Korean herbal formulation, Honghwain-Jahage (HJ), which is comprised of a herb of Carthamus tinctorius L. seed and Hominis Placenta, was investigated for inhibiting effects on IL-1 beta-stimulated bone resorption in the fetal mouse bone culture system. Results of in vitro cytotoxicities showed that HJ extracts have no any cytotoxicities in concentrations of 1-200 microg/ml on the cultured osteoblast cells derived from mouse calvarial bone explants. Cell viability was not significantly affected by treatment with the indicated concentration of the extracts. The HJ extracts were shown to have inhibitory effects against the synthesis of PGE(2). We also examined the effect of the pretreatment with various concentrations of the HJ extracts then treated by the PGE(2)-induction agents. Pretreatment of the HJ extracts for 1 h, which by itself had little effect on cell survival, reduced the synthesis of PGE(2). Furthermore, the HJ extracts were shown to have protective effects against plasminogen dependent fibrinolysis induced by IL-1 beta. Pretreatment of the HJ extracts for 1 h did not enhance the plasminogen dependent fibrinolysis. Finally, co-treatment of HJ with calcitonin showed significant inhibitory activity on the IL-1 beta-stimulated bone resorption. From these results, it was found that HJ extracts inhibited IL-1 beta-induced bone resorption.

Animals↗
PubMed2000

Direct and indirect actions of fibroblast growth factor 2 on osteoclastic bone resorption in cultures.

Fibroblast growth factor 2 (FGF-2 or basic FGF) is known to show variable actions on bone formation and bone resorption. This study was undertaken to elucidate the mechanisms whereby FGF-2 affects bone metabolism, especially bone resorption, using three different culture systems. FGF-2 at 10(-9) M and higher concentrations induced osteoclastic cell formation in the coculture system of mouse osteoblastic cells and bone marrow cells, and this induction was abrogated by nonsteroidal anti-inflammatory drugs (NSAIDs). 45Ca release from prelabeled cultured mouse calvariae stimulated by FGF-2 (10(-8) M) was also inhibited by NSAIDs, and the inhibition was stronger by NSAIDs, which are more selective for inhibition of cyclooxygenase 2 (COX-2) than COX-1, suggesting the mediation of COX-2 induction. COX-2 was highly expressed and its messenger RNA (mRNA) level was stimulated by FGF-2 in osteoblastic cells whereas it was undetectable or not stimulated by FGF-2 in cells of osteoclast lineage. To further investigate the direct actions of FGF-2 on osteoclasts, resorbed pit formation was compared between cultures of purified osteoclasts and unfractionated bone cells from rabbit long bones. FGF-2 (> or = 10(-12) M) stimulated resorbed pit formation by purified osteoclasts with a maximum effect of 2.0-fold at 10(-11) M, and no further stimulation was observed at higher concentrations. However, FGF-2 at 10(-9) M - 10(-8) M stimulated resorbed pit formation by unfractionated bone cells up to 9.7-fold. NS-398, a specific COX-2 inhibitor, did not affect the FGF-2 stimulation on purified osteoclasts but inhibited that on unfractionated bone cells. We conclude that FGF-2 at low concentrations (> or =10(-12) M) acts directly on mature osteoclasts to resorb bone moderately, whereas at high concentrations (> or = 10(-9) M) it acts on osteoblastic cells to induce COX-2 and stimulates bone resorption potently.

Acid Phosphatase↗
PubMed1994

Effects of interleukin-2 on bone resorption and natural immunity in osteopetrotic (ia) rats.

Cells of the immune system and the cytokines they produce have been shown to function in the regulation of bone turnover. Incisors absent (ia) osteopetrotic rats demonstrate defects in natural immunity and bone resorption, even though they have excess numbers of both natural killer (NK) cells and osteoclasts. In an attempt to correct these defects, mutant (ia) and normal rats were infused with 3 x 10(4)U recombinant interleukin-2 (rIL-2)/day for 14 days using osmotic minipumps. The effects of IL-2 on natural immune function and bone resorption were evaluated after the infusion period. The percentage of NK cells in the spleen after treatment was quantitated by phenotypic analysis using monoclonal antibodies and flow cytometry. The elevated levels of NK cells normally seen in ia mutants were reduced to normal in the IL-2-infused rats. NK cell activity was evaluated by the 51Cr release assay and found to be enhanced to normal killing levels in the IL-2-treated mutants. The defects in NK function are corrected by IL-2 therapy. Likewise, the bone resorption defect appears to be corrected by the IL-2 infusions. The bone marrow cavity size was significantly increased in the IL-2-treated mutants compared with control mutants. Additionally, the percentage of osteoclasts exhibiting normal morphology was significantly increased in the IL-2-treated mutants. The bone density of the caudal vertebrae, evaluated by gray-scale analysis of x-rays, was found to be reduced in the IL-2-treated mutants. Interleukin-2 corrects both the bone resorption and natural immune defects in the ia mutation.

Animals↗
PubMed2004

Roles of hyaluronan in bone resorption.

BACKGROUND: Hyaluronan, an unsulfated glycosaminoglycan, while being closely linked to osteoclast function several years ago, has received little attention lately. Given recent new knowledge of hyaluronan's possible cell binding abilities, it is important to re-examine the role of this polysaccharide in bone homeostasis. DISCUSSION: Previously published data demonstrating a linkage between induction of hyaluronan synthesis and osteoclast-mediated bone resorption are reviewed. Suggestions are made involving the cell binding ability of hyaluronan and its potential to mediate osteoclast binding to bone surfaces and its potential to serve as a diffusion barrier and participate in the sealing zone required for osteoclast-mediated bone resorption. SUMMARY: This brief article summarizes previous studies linking HA to bone resorption and suggests roles for hyaluronan in the process of bone resorption.

Animals↗
PubMed2003

Various selected vegetables, fruits, mushrooms and red wine residue inhibit bone resorption in rats.

To make a broad survey of the effect of components of the human diet on bone resorption, a few items from the following categories were added to rat diets: vegetables, fruits, beans, nuts and seeds, mushrooms, carbohydrate sources and beverages. The effect on bone resorption was measured by the urinary excretion of tritium released from bones of 9-wk-old rats prelabeled with tritiated tetracycline from weeks 1 to 6. The number of rats per experiment was 26--6, 5, 5, 5 and 5 in the untreated control group fed the plain semipurified diet, the positive control group fed onions and three groups fed one of the newly investigated items, respectively. New experiments were added until 10 rats were fed each item in each of two separate experiments. The results for each item were compared to those for the untreated control group (n = 12) investigated simultaneously. We found that feeding rats 1 g/d of dry fennel, celeriac, oranges, prunes, French beans and farmed and wild mushrooms (Agaricus hortensis and Boletus edulis) as well as the freeze-dried residue from red wine significantly (P < 0.05 or lower) inhibited bone resorption. Eighteen items had no significant effect. To date we have found 25/53 items that exhibit inhibitory activity. Activity appears to be restricted to the following categories: vegetables, salads, herbs, mushrooms, fruits and red wine residue (25/36 items effective). Furthermore, as assessed in a similar experimental design with various doses of a mixture of active items, we determined the minimum effective dose of the dry items to be 170 mg/d. These results open the possibility for targeted interventions in humans.

Agaricales↗
PubMed2006

Bone resorption markers in vitamin D insufficiency.

Severe vitamin D deficiency (serum 25 hydroxyvitamin D (25(OH)D) below 12.5 nmol/L) causes rickets and osteomalacia, but there is good evidence that lesser degrees of hypovitaminosis D (vitamin D insufficiency) have deleterious effects on bone and other organs. Evidence of impaired mineralization, suggestive of vitamin D insufficiency, has been found in bone biopsies of hip fracture patients in the UK, and several studies around the world have shown a rise in serum parathyroid hormone (PTH) as 25(OH)D levels fall below 50 nmol/L. Fifty-seven percent of hospital inpatients in a Boston study had vitamin D insufficiency and their serum 25(OH)D showed an inverse relationship to their serum alkaline phosphatase (ALP) levels. Thirty-five percent of outpatients had vitamin D insufficiency in an Adelaide study, where ALP and urine hydroxyproline and pyridinium cross-links were all inversely related to serum 25(OH)D. The increased bone resorption of vitamin D insufficiency is important on two counts. Firstly, increased bone resorption may lead to increased bone loss and osteoporosis and, secondly, increased turnover appears to increase fracture risk in its own right. A consensus is developing that serum 25(OH)D levels should be maintained at 50 nmol/L or greater in the elderly to minimize the occurrence of fractures. In addition, it appears that optimal levels of bone resorption markers in this population are at or just below the mean level for premenopausal women.

Biomarkers↗
PubMed1987

Tumor necrosis factor-alpha (cachectin) stimulates bone resorption in mouse calvaria via a prostaglandin-mediated mechanism.

Recombinant human (h) and murine (m) tumor necrosis factor (TNF)-alpha stimulated bone resorption and the production of prostaglandin (PG) E2 in neonatal mouse calvaria in organ culture. In experiments of 72-h duration, the effect on bone resorption was of large magnitude (an average increase in medium calcium of 3.3 mg/dl above control values in 11 separate experiments) and occurred over a concentration range of 0.1-20 ng/ml mTNF and 0.5-50 ng/ml hTNF. Accompanying the TNF-enhanced release of bone calcium there was enhanced accumulation of PGE2 in the culture medium. The increases in medium calcium and PGE2 were both inhibited completely by nontoxic concentrations of 4 different PG cyclooxygenase inhibitors (indomethacin, piroxicam, ibuprofen, and acetylsalicylic acid) but not by the noncyclooxygenase inhibitor salicylic acid. The magnitude of the PGE2 response, but not the calcium release, was less for bones treated with TNF than for those treated with equipotent doses of epidermal growth factor or human transforming growth factors-alpha or -beta, suggesting that the local site of production of PGE2 in bone may be different for TNF than for the other factors. Repeated sc injections of hTNF to intact mice for a 48-h period produced a statistically significant elevation of the plasma calcium concentration. Because TNF is produced by cells of the monocyte/macrophage lineage in response to invasive stimuli such as the presence of tumor, our findings indicate that a host factor produced in response to malignant cells can cause enhanced bone resorption. Thus, the concept of the humoral hypercalcemias of malignancy must be expanded to include mediators not produced by the tumor cells themselves.

Animals↗
PubMed1993

Evidence that interleukin-1 mediates its effects on bone resorption via the 80 kilodalton interleukin-1 receptor.

Interleukin-1 (IL-1) mediates its effects through two distinct receptors, one of 80 kilodaltons (80 kD) present in athymic lymphocytes and fibroblasts, and one of 60 kD present in cells of the monocyte-macrophage lineage. A novel monocyte cytokine in the IL-1 family which binds to both the 80 and the 60 kD receptors has been purified, cloned, and expressed. As the interleukin-1 receptor antagonist (IL-1ra) has been shown to inhibit bone resorption in organ culture, it is not clear whether these effects are mediated through the 80 or the 60 kD receptor. Recently, neutralizing antibodies (35F5) have been developed to the 80 kD receptor which inhibit IL-1 effects mediated through this receptor. To determine the importance of the 80 kD receptor to IL-1-mediated bone resorption, we used the neutralizing antibodies (35F5) to the 80 kD receptor to determine if they inhibited bone resorption stimulated by IL-1 in bone organ cultures. The 35F5 antibody blocked bone-resorbing activity due to IL-1 completely, and also blocked control or "endogenous" bone-resorbing activity present in murine bone organ cultures incubated in control media. The 35F5 antibody had no effect on bone resorption mediated by tumor necrosis factor (TNF), or parathyroid hormone (PTH). These data suggest that the availability of the 80 kD IL-1 receptor is required for osteoclastic bone resorption mediated by IL-1.

Animals↗
PubMed1981

Delayed stimulatory effect of cyclic AMP on bone resorption in vitro.

The effect of dibutyryl cyclic AMP (dbcAMP) and the phosphodiesterase inhibitors 3-isobutyl methylxanthine (IBMX) and theophylline on bone resorption was studied in an organ culture system for 96-114 h using half calvaria from 6-7 day old mice. The magnitude of resorption was assessed by measuring the release from the bones of previously incorporated 45Ca. It was observed that dbcAMP, IBMX and theophylline, following a lag period or a period of reduced bone resorption, all progressively increased mineral mobilization. Although the continuous presence of dbcAMP increased mineral mobilization more than a temporary exposure, a limited treatment of 24 h with the nucleotide was sufficient to bring about the delayed stimulatory response. It is concluded that the observations support our earlier proposal that cAMP is not a mediator of the early stages of parathyroid hormone (PTH)- and prostaglandin E2 (PGE2)-stimulated bone resorption. We suggest that the role played by cAMP may be related to the capacity of PTH and PGE2 to develop new osteoclasts, a phenomenon which takes more than 24 h to be observed.

1-Methyl-3-isobutylxanthine↗
PubMed1975

Acute inhibition of mineralization and stimulation of bone resorption mediated by hypophosphatemia.

Using rats previously labeled with 45Ca, the effects of a severely phosphate deficient diet on calcium mobilization from bone into serum were examined in both intact and thyroparathyroidectomized (TPTX) RATS. With the TPTX animals, increased calcium mobilization from bone was evident 12 hr after the rats had been placed on the low phosphorus diet. At that time period, both TPTX and intact rats had become severely hypophosphatemic. However, in intact rats, calcium mobilization was not observed until 48 hr had elapsed. Both intact and TPTX hypophosphatemic rats developed hypercalcemia. To determine if inhibition of calcium deposition into bone contributed to this change, the course of 45Ca movement from blood into bone was followed in an experiment where rats received a single injection of the isotope at the time the low phosphorus diet was given. The animals on the low phosphorus diet showed a significantly lower bone specific activity and a higher serum specific activity compared to the control group, indicating calcium deposition into bone was inhibited. We conclude that the acute response to hypophosphatemia, resulting from the low phosphorus dietary regimen, was an increase in bone resorption and an inhibition of bone mineralization. The increase in bone resorption occurred more rapidly in TPTX rats than in the intact animals.

Animals↗
PubMed2000

Decreased nitric oxide levels stimulate osteoclastogenesis and bone resorption both in vitro and in vivo on the chick chorioallantoic membrane in association with neoangiogenesis.

High nitric oxide (NO) levels inhibit osteoclast (OC)-mediated bone resorption in vivo and in vitro, and nitrate donors protect against estrogen-deficient bone loss in postmenopausal women. Conversely, decreased NO production potentiates OC bone resorption in vitro and is associated with in vivo bone loss in rats and humans. Previously, we reported that bone sections from rats administered aminoguanidine (AG), a selective inhibitor of NO production via inducible NO synthase, exhibited both increased OC resorptive activity as well as greater numbers of OC. Here, we investigated further whether AG promoted osteoclastogenesis, in addition to stimulating mature OC function, using a modified in vivo chick chorioallantoic membrane (CAM) system and an in vitro chick bone marrow OC-like cell developmental model. AG, focally administered in small agarose plugs placed directly adjacent to a bone chip implanted on the CAM, dose-dependently elicited neoangiogenesis while stimulating the number, size, and bone pit resorptive activity of individual OC ectopically formed in vivo. In addition to enhancing OC precursor recruitment via neoangiogenesis, AG also exerted other vascular-independent effects on osteoclastogenesis. Thus, AG promoted the in vitro fusion and formation from bone marrow precursor cells of larger OC-like cells that contained more nuclei per cell and exhibited multiple OC differentiation markers. AG stimulated development was inversely correlated with declining medium nitrite levels. In contrast, three different NO donors each dose-dependently inhibited in vitro OC-like cell development while raising medium nitrite levels. Therefore, NO sensitively regulates OC-mediated bone resorption through affecting OC recruitment (angiogenesis), formation (fusion and differentiation), and bone resorptive activity in vitro and in vivo. Possibly, the stimulation of neoangiogenesis and OC-mediated bone remodeling via AG or other pro-angiogenic agents may find clinical applications in reconstructive surgery, fracture repair, or the treatment of avascular necrosis.

Acid Phosphatase↗
PubMed2002

[Comparative study of bone resorption markers for the diagnosis of bone metastasis in lung cancer].

NTx and I CTP, a metabolite of type I collagen, were compared as to their usefulness as indicators of bone metastasis in lung cancer. The NTx level was significantly higher in lung cancer patients with bone metastasis (107.9 +/- 56.1 nM BCE/mM) than in those without it (p < 0.0001), as was the I CTP level (10.0 +/- 6.5 ng/ml; p < 0.0001). The Z scores of NTx and I CTP were 2.37 and 2.04, respectively, indicating that NTx is superior to I CTP in sensitivity to bone metastasis because of its higher Z score and its higher area under the ROC curve. The cutoff values of these markers were set to produce the highest accuracy/sensitivity rates and to make possible the highest diagnostic efficiency, and then the odds ratios at these cutoff values were calculated. The odds ratios of NTx and I CTP at cutoff values for the highest accuracy were 66.3 and 12.6, respectively; those offering the highest diagnostic efficiency were 46.5 and 10.0, respectively. These results indicated that NTx offers better prediction of bone metastasis in lung cancer than does I CTP.

Biomarkers, Tumor↗