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 1,045 records · Page 58Linked to original sources
PubMed1992

Human cystatin C, a cysteine proteinase inhibitor, inhibits bone resorption in vitro stimulated by parathyroid hormone and parathyroid hormone-related peptide of malignancy.

The effect of human recombinant cystatin C, a cysteine proteinase inhibitor, on bone resorption in vitro was evaluated. Bone resorption was assessed by analyzing the release of 45Ca and 3H from mouse calvarial bones prelabeled in vivo by injections with 45Ca or [3H]proline, respectively. In 24 h cultures, cystatin C (50 micrograms/ml) significantly inhibited the release of 45Ca and 3H stimulated by parathyroid hormone (PTH, 15 nmol/liter) or parathyroid hormone-related peptide of malignancy (PTHrP, 15 nmol/liter). The degree of inhibition caused by cystatin C in these 24 h cultures was similar to that caused by calcitonin (30 ng/ml). The inhibitory effect of cystatin C on 45Ca release induced by PTH was sustained in 96 h cultures, whereas the initial inhibition caused by calcitonin was transient. Cystatin C, 10-100 micrograms/ml, caused a dose-dependent inhibition of PTH (15 nmol/liter), and PTHrP (15 nmol/liter) stimulated 45Ca release. Addition of 50 micrograms/ml of cystatin C to mouse bone cultures inhibited the release of 45Ca induced by PTH and PTHrP at a wide range of submaximal and maximal concentrations of hormones (0.01-10 nmol/liter). No effect of cystatin C on 45Ca release in dead bones could be observed, nor did the inhibitor decrease the release of calcium in control bones. The inhibition by cystatin C on PTH-induced mineral mobilization was reversible. Cystatin C (1-100 micrograms/ml) did not affect protein synthesis or mitotic activities in mouse calvarial bones as assessed by the incorporation of [3H]proline and [3H]thymidine, respectively. These data show that cystatin C is a potent inhibitor of mineral mobilization and matrix degradation in cultured bones stimulated to resorb by PTH and PTHrP and that this effect is not due to general cytotoxicity.

Bone Resorption↗
PubMed1983

Induction of monocytic differentiation and bone resorption by 1,25-dihydroxyvitamin D3.

1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] stimulates bone resorption in man and other vertebrates, in part, by increasing the number of osteoclasts, the principal resorbing cells of bone. Because osteoclasts are very likely derived from a member(s) of the mononuclear phagocyte family, we determined if 1,25(OH)2D3 promotes maturation of these cells by studying its effects on the human promyelocytic leukemia cell line HL-60. Of the vitamin D3 metabolites tested, only 1,25(OH)2D3, at 10(-10) to 10(-7) M, induces the differentiation of HL60 into mono- and multinucleated macrophage-like cells. Phenotypic change is evident within 24 hr and reaches a plateau between 72 and 96 hr of incubation. The changes are metabolite-specific and include (i) adherence to substrate, (ii) acquisition of the morphological features of mature monocytes, (iii) a 4- to 6-fold enhancement in lysozyme synthesis and secretion, (iv) increase in the fraction of alpha-naphthyl acetate esterase-positive cells from approximately 2% to 100% of the population, and (v) the acquisition of several monocyte-associated cell surface antigens. More importantly, treated HL-60 cells acquire the capacity to bind and degrade bone matrix, two of the essential, functional characteristics of osteoclasts and related bone-resorbing cells. These results, considered together with the reported action of 1,25(OH)2D3 on nontransformed mononuclear cells, are consistent with the view that vitamin D3 enhances bone resorption and osteoclastogenesis in vivo by promoting the differentiation of precursor cells.

Animals↗
PubMed1976

Effect of adrenal steroids on bone resorption in rats.

Rats labeled with strontium-85 (85Sr) were rejected with adrenocortical steroids for 2 wk. The urinary-to-tibial (U/T) 85Sr ratio was used as an index of bone resorption. The glucocorticoids caused an inhibition of skeletal resorption, as judged by the 50% reduction in the U/T ratio, and decreased excretion of hydroxyproline. Thyroidal calcitonin levels were slightly elevated in glucocorticoid-treated animals, suggestive of a possible retardation of calcitonin release. The U/T ratios of thyroparathyroidectomized (TPTX) rats injected with corticosteroids were 50% of control values. The results indicate that glucocorticoids inhibit bone resorption independent of the action of calcitonin. Cortisol treatment increased the tibial density as measured by a radiographic technique. However, bone density was decreased and the U/T ratio increased in steroid-treated rats fed a low-calcium diet. In TPTX cortisol-treated rats, parathyroid extract (PTE) increased the U/T ratio and serum calcium but not to the degree observed in TPTX PTE-injected control animals. These experiments indicate that in rats glucocorticoids inhibit the rate of bone resorption but this effect can be overcome in part by PTE.

Animals↗
PubMed2005

Citrate reverses cyclosporin A-induced metabolic acidosis and bone resorption in rats.

BACKGROUND: Cyclosporine A (CsA) causes distal renal tubular acidosis (RTA) and osteoporosis. We have recently reported that the reduction of nitric oxide (NO) exacerbates this condition. Distal RTA may deplete bone mineral due to the chronic buffering of acid in the blood. The interaction of CsA and NO in causing metabolic acidosis and bone demineralization has not been studied previously. Nor has the salubrious effect of citrate therapy. PURPOSE: To examine the effect of systemic pH correction by citrate on renal electrolyte (Na, K, Cl, NH3, HCO3) excretion following acute water loading in CsA-treated and NO-reduced rats. We further evaluated femoral bone density and bone demineralization activity after the same treatments. METHODS: Rats received CsA, L-arginine (L-Arg), or nitro-L-arginine-methyl ester (L-NAME), or a combination of CsA+L-NAME plus or minus citrate. Urine and blood electrolytes were examined, as well as the urine excretion of deoxypyridinoline and the bone density of both femurs. RESULTS: CsA and L-NAME reduced urine pH and the serum HCO3- concentration, and increased serum K+ and Cl- concentrations. The combination of CsA with L-NAME caused more severe deficits in the serum HCO3- concentration and elevations in serum K+ and Cl- concentrations than either drug alone. Both CsA and L-NAME reduced urinary nitrate excretion, which was reversed by co-administration of L-Arg. Co-administration of citrate or L-Arg improved the CsA- and L-NAME-induced acidosis and hyperkalemia. Bone resorption and density of the femurs were decreased by CsA and L-NAME and were additive for both drugs. Co-administration of citrate or L-Arg restored both bone resorption and density to normal levels. CONCLUSION: CsA induces a hyperchloremic metabolic acidosis with hyperkalemia and a reduction in NO. The ensuing systemic acidosis causes bone resorption and demineralization. These effects were corrected by co-treatment with citrate. Citrate, at least in part, directly reduces the protonation of bone in animals treated with CsA and is recommended as a potential adjunct drug to prevent bone demineralization in patients chronically receiving CsA.

Acidosis↗
PubMed1987

The Walker 256/B carcinosarcoma in thyroparathyroidectomized rats: a model to evaluate inhibitors of bone resorption.

The Walker 256/B mammary carcinosarcoma implanted in male Fischer rats was used to evaluate bone resorption inhibitors. The model was improved by thyroparathyroidectomizing the animals to avoid counter-regulation by parathyroid hormone or calcitonin, by pair-feeding them, and by using 2 hour fasting calciuria as a resorption index to minimize the influence of differences in growth or in intestinal calcium absorption. Over a 10 day period, the control animals displayed a progressive increase of plasma calcium (Ca) and fasting urinary Ca excretion, a decrease of plasma phosphate, and an increase of urinary phosphate excretion. Osteocalcin did not change. The daily administration of dichloromethylene bisphosphonate (Cl2MBP) totally prevented the increase of fasting urinary Ca excretion, whereas plasma Ca remained at a higher level than thyroparathyroidectomized (TPTX) control rats. Osteocalcin decreased. Two new aminobisphosphonates, 4-amino-1-hydroxybutylidene-1,1-bisphosphonate (AHBuBP), and 6-amino-1-hydroxyhexylidene-1,1-bisphosphonate (AHHexBP) had a similar effect. The order of potency shown by the three bisphosphonates was similar to that reported using the metaphyseal bone density evaluation method in growing rats: AHBuBP greater than AHHexBP greater than Cl2MBP, the difference each time being one order of magnitude. The analysis of the relationship between urinary and plasma values in tumor-bearing animals suggested an increased renal tubular reabsorption of Ca and a decreased reabsorption of phosphate (Pi). Therefore, in this model of malignant osteolysis, urinary Ca excretion is the best marker for bone resorption.

Animals↗
PubMed1986

Comparison of the mechanisms of bone resorption induced by 1 alpha,25-dihydroxyvitamin D3 and lipopolysaccharides.

The mechanisms of increase in bone resorption induced by 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3] and bacterial lipopolysaccharides (LPS) were compared in an in vitro dead bone assay and a living bone assay. 1 alpha,25(OH)2D3 at concentrations of 0.05-5 ng/ml dose-dependently enhanced the ability of alveolar macrophages to release 45Ca from prelabeled dead bone particles (dead bone assay). In addition, the vitamin promoted fusion of the macrophages to form multinucleated cells and also enhanced glucose consumption, a marker of activation of macrophages. LPS at 0.05-5 micrograms/ml similarly enhanced the release of 45Ca from the dead bone particles and glucose consumption by alveolar macrophages, but it did not induce fusion of the cells at any concentration. Both 1 alpha,25(OH)2D3 and LPS dose-dependently stimulated the release of 45Ca from fetal mouse calvaria prelabeled with 45Ca (living bone assay). Compared to control bone, there were several times as many osteoclasts per given length of trabecular bone surface in calvaria treated for 5 days with either 5 ng/ml of 1 alpha,25(OH)2D3 or 5 micrograms/ml of LPS. Indomethacin (10(-5) M) completely inhibited the LPD-induced increase of osteoclasts, but not the 1 alpha,25(OH)2D3-induced increase. These results suggest that 1 alpha,25(OH)2D3 and LPS similarly stimulate bone resorption by activating macrophages as well as by promoting fusion of precursor cells to form multinucleated cells. 1 alpha,25(OH)2D3 induced formation of multinucleated cells with bone-resorbing activity directly, whereas LPS appeared to induce multinucleated cells through prostaglandin synthesis by some other types of cells present in living bone tissues.

Animals↗
PubMed1968

On the mechanisms of bone resorption. The action of parathyroid hormone on the excretion and synthesis of lysosomal enzymes and on the extracellular release of acid by bone cells.

Bone resorption, characterized by the solubilization of both the mineral and the organic components of the osseous matrix, was obtained in tissue culture under the action of parathyroid hormone (PTH). It was accompanied by the excretion of six lysosomal acid hydrolases, which was in good correlation with the progress of the resorption evaluated by the release of phosphate, calcium 45 or hydroxyproline from the explants; there was no increased excretion of two nonlysosomal enzymes, alkaline phosphatase, and catalase. Balance studies and experiments with inhibitors of protein synthesis indicated that the intracellular stores of the acid hydrolases excreted were maintained by new synthesis. The release was not due to a direct disruption of the lysosomal membrane by PTH; it is presumed to result from an exocytosis of the whole lysosomal content and to involve mechanisms similar to those controlling the secretion of this content into digestive vacuoles. The resorbing explants acidified their culture fluids at a faster rate and released more lactate and citrate than the controls; this release was in good correlation, in the PTH-treated cultures, with the resorption of the bone mineral, but the amount of citrate released was considerably smaller than that of lactate. The acid released could account for the resorption of the mineral. It is proposed, as a working hypothesis, that the acid hydrolases of the lysosomes are active in the resorption of the organic matrix of bone and that acid, originating possibly from the stimulation of glycolysis, cares for the concomitant solubilization of bone mineral while also favoring the hydrolytic action of the lysosomal enzymes.

Acids↗
PubMed2003

[The OPG/RANKL/RANK system and bone resorptive disease].

The OPG/RANKL/RANK system plays an important role in osteoclastogenesis and represents a great progress in bone biology. RANKL, which expresses on the surface of osteoblast/stromal cells and activated T cells, binds to RANK on the osteoclastic precursors or mature osteoclasts, and promotes osteoclastogenesis and bone resorption. While osteoprotegerin (OPG), which is expressed by osteoblasts/stromal cells, strongly inhibits bone resorption by binding to its ligand RANKL and thereby blocks the interaction between BANKL and RANK. A number of cytokines and hormones exert their effects on bone metabolism by regulating the OPG/RANKL ratio in the bone marrow microenvironment. RANK is also expressed on mammary epithelial cells and RANKL expression in these cells is induced by pregnancy hormones, RANKL and RANK are essential for the formation of the lactating mammary gland and the transmission of maternal calcium to neonates in mammalian species. Modulation of these systems provides a unique opportunity to develop novel therapeutics to inhibit bone loss in osteoporosis, rheumatoid arthritis, and bone metastasis of cancer. Further research should be focused on the cooperation of OPG/RANKL/RANK system with other signal pathways and the interactions among bone remodeling, immune system and endocrinology system. Currently, the development of OPG analogues or compounds which may stimulate OPG expression is becoming an attractive industry which may be profitable to both patients and manufacturers.

Animals↗
PubMed1993

The effect of ovariectomy on periosteal bone formation and bone resorption in adult rats.

In order to quantify the rate of bone metabolism after ovariectomy, tetracycline was injected intraperitoneally into 3-month-old female Wistar rats to label the mineralizing front and ovariectomy was performed. The rats were sacrificed 91 days later, whereupon serum calcium and phosphorus were determined. The femurs were sectioned in the upper part, photographed and the area between the tetracycline line and the outer perimeter of the bone was planimetered at a reference point. The area of periosteal bone formed was noted to be 28.3% greater than in control rats (P = 0.0002) and the area of the medullary cavity 18.8% larger (P = 0.033), indicating enhanced osteoblast and osteoclast function. The serum calcium concentration was unchanged, but a significant reduction in phosphorus was seen in the ovariectomized rats (P < 0.0001). The data suggest that the stimulated bone formation is a representative phenomenon in ovariectomized rats at least for 100 days and bone resorption remains elevated in the course of processes possibly leading to osteoporosis.

Animals↗
PubMed1986

Simultaneous measurement of bone resorption and collagen synthesis in neonatal mouse calvaria.

A tissue culture technique which permits the simultaneous measurement of collagen synthesis and bone resorption has been developed. Cultured neonatal mouse calvaria undergo resorption when stimulated by a number of agents including parathyroid hormone, vitamin D, and prostaglandin E2. Mouse calvaria are of sufficient size to measure the extent of proline incorporation into collagenase-digestible protein. Four chemically diverse stimulators of bone resorption were tested for their effect on collagen synthesis. For each stimulator tested, the dose-response relationships for the stimulation of resorption and the inhibition of collagen synthesis were found to coincide.

Animals↗
PubMed1997

Longitudinal evaluation of a bone resorption marker in elderly subjects.

The variability over time in the excretion of a bone resorption metabolite (collagen type I N-telopeptide crosslink, NTx) was evaluated in a cohort of community-dwelling elderly men and women (mean age 73 years). Three annual 24-h urine samples were collected. NTx concentration was measured using an established ELISA. Total (24-h) NTx excretion as well as Ntx/creatinine concentration were compared. Men had a significantly lower excretion of NTx/creatinine than women who were not on hormone replacement therapy. Overall, the within-subject long-term coefficient of variability for Ntx/creatinine was 26%. The correlation coefficient between the samples taken a year apart was higher for the 24-h NTx excretion (r = 0.66) than for the 24-h creatinine excretion (r = 0.51). The consistency of NTx excretion over time was also evaluated in all 93 subjects with three yearly samples using Kendall's rank correlation method; the resulting coefficient of concordance was 0.78 (significant at the 0.01 level). These results indicate that while NTx excretion varies in subject samples collected over a period of 2 years, this variability is not much greater than the daily variation reported for NTx and other bone metabolism markers. The relative reproducibility of NTx excretion over time in this age group was also evident in the coefficient of concordance. The results provide support for stratifying subjects according to level of bone resorption and identifying those subjects with high turnover who may be at greater risk of osteoporotic fracture.

Aged↗
PubMed1999

Reference value for urinary deoxypyridinoline as a specific marker for measuring bone resorption in Thais.

In the next century, the increasing number of elderly and rising healthcare costs will bring with it metabolic bone problems, particularly osteoporosis. Deoxypyridinoline: Dpd in urine is a sensitive and specific marker for screening and monitoring of bone resorption in a variety of diseases affecting bone turnover and in risk groups especially in the postmenopause. The reference value among aging (21-60 years) of a healthy well defined group was studied by collecting the urine between 700-1000 hours and using the ELISA technique to determine the level of Dpd. The reference value of Dpd in 113 males and 298 females 1.3-6.5 and 1.5-6.9 nm Dpd/nm Creatinine respectively. The level of Dpd in females was significantly higher than in males at p < 0.028. However, the average value of deoxypyridinoline in postmenopause was higher than premenopause but not different at p = 0.05. There are many factors which influence the results so the overall reference value is only a guideline for screening in bone resorption.

Adult↗
PubMed1995

Measurement of bone resorption by strontium excretion in prelabelled rats.

The body handles strontium (Sr) in a similar way to calcium (Ca) in that Sr is absorbed by the gut, concentrated in bone and excreted in urine and feces. In this study, rats were labelled with Sr during growth and later subjected to various treatments affecting bone resorption and Sr excretion was measured during and after treatment. Six weeks old Wistar rats were repeatedly s.c. injected with SrCl2. After a period of 2 weeks after the last Sr injection the rats were subjected to various treatments. Sr clearance was then measured weekly for 2 weeks. In the first experiment, the Sr labelled rats were sham-operated (sham) or ovariectomized (ovx) and urine collected afterwards. Sham rats were either treated with 4 daily s.c. clodronat injections at the beginning of the urine sampling, fed a low Ca diet (0.08% Ca) during the second sampling week or injected with saline. Urinary Sr excretion was decreased in the clodronate group during the first sampling week and increased in the Ca depleted group during feeding the low Ca diet. Sr excretion by ovx rats was similar to the sham control. In the second experiment, the effect of high-dose treatment with 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) or clodronate on bone resorption induced by Ca depletion was assessed by Sr output in urine and feces. Sr labelled rats were fed a low Ca diet and daily injected with 24,25(OH)2D3 or clodronate for 14 consecutive days. Clodronate significantly decreased Sr output during both sampling weeks. Treatment with 24,25(OH)2D3 resulted in an increased Sr output indicating an increase in bone resorption.

24,25-Dihydroxyvitamin D 3↗
PubMed1999

Osteopontin-deficient mice are resistant to ovariectomy-induced bone resorption.

Osteopontin is one of the major noncollagenous bone matrix proteins produced by osteoblasts and osteoclasts, bone cells that are uniquely responsible for the remodeling of mineralized tissues. Osteoclasts express the alphavbeta3 integrin, which is one of the receptors for osteopontin. Recent knockout studies revealed that noncollagenous bone matrix proteins are functionally important in regulation of bone metabolism. However, the significance of the presence of osteopontin in in vivo has not been known. We report here that osteopontin knockout mice are resistant to ovariectomy-induced bone resorption compared with wild-type mice. Microcomputed tomography analysis indicated about 60% reduction in bone volume by ovariectomy in wild-type mice, whereas the osteopontin-deficient mice exhibited only about 10% reduction in trabecular bone volume after ovariectomy. Reduction in uterine weight was observed similarly in both wild-type and osteopontin-deficient mice, indicating the specificity of the effect of osteopontin deficiency on bone metabolism. We propose that osteopontin is essential for postmenopausal osteoporosis in women. Strategies to counteract osteopontin's action may prove effective in suppressing osteoporosis.

Animals↗
PubMed1997

Cortical bone resorption in osteoporosis.

A study was made of 110 women: 35 healthy premenopausal, 40 healthy postmenopausal, and 35 women diagnosed as having postmenopausal osteoporosis. The postmenopausal women had similar ages and years since menopause (YSM). In all of the women, total bone mass was evaluated by dual-energy X-ray absorptiometry and metacarpal morphometry was evaluated by radiogrammetry on the second metacarpal of the nondominant hand, performed by computed radiography. An external metacarpal diameter of >/=7.4 mm was required as proof of having developed an adequate peak bone mass. The endosteal diameter, which is indicative of bone resorption in both groups of postmenopausal women, obtained in the postmenopausal groups was subtracted from the endosteal diameter obtained in the premenopausal group and the resulting figure was divided by the years since menopause to calculate the rate of cortical bone resorption/year for each group. The endosteal diameters values differed in the three groups studied (P < 0.0001): 3.2 +/- 0.7 mm in the healthy premenopausal women; 3.9 +/- 0.6 mm in the healthy postmenopausal women; and 4.7 +/- 0.5 mm in the osteoporotic postmenopausal women. The rate of cortical bone resorption was 0.068 +/- 0.002 mm/YSM (years since menopause) in the osteoporotic postmenopausal women and 0.033 +/- 0.003 mm/YSM in the healthy postmenopausal women (P < 0. 0001). These figures reflect the importance of bone resorption, as opposed to deficient bone formation, as a cause of osteoporosis.

Absorptiometry, Photon↗
PubMed2005

Inhibition of hormone and cytokine-stimulated osteoclastogenesis and bone resorption by interleukin-4 and interleukin-13 is associated with increased osteoprotegerin and decreased RANKL and RANK in a STAT6-dependent pathway.

Interleukin (IL)-4 and IL-13 are cytokines that inhibit bone resorption. Data showing an inhibitory effect of IL-4 and IL-13 on RANK mRNA in mouse calvariae were first reported at the 22nd American Society for Bone and Mineral Research Meeting (Lerner, U.H., and Conaway, H. H. 2000) J. Bone Min. Res. 15, Suppl. 1, Abstr. SU 230). In the present study, release of 45Ca from cultured mouse calvarial bones stimulated by different cytokines, peptides, and steroid hormones was inhibited by IL-4 and IL-13. IL-4 and IL-13 decreased receptor activator of nuclear factor-kappaB ligand (RANKL) and RANK mRNA and increased osteoprotegerin (OPG) mRNA in calvariae. Additionally, the cytokines decreased RANKL protein and increased OPG protein in calvarial bones. In osteoblasts isolated from calvariae, both an increase in RANKL mRNA and a decrease in OPG mRNA and protein elicited by vitamin D3 were reversed by IL-4 and IL-13. IL-4 and IL-13 decreased the number of tartrate-resistant acid phosphatase positive multinucleated cells and the mRNA expression of calcitonin receptor, tartrate-resistant acid phosphatase, and cathepsin K in mouse spleen cells and bone marrow macrophages (BMM) treated with macrophage colony-stimulating factor and RANKL. Inhibition of mRNA for RANK and the transcription factor NFAT2 was also noted in spleen cell and BMM cultures treated with IL-4 and IL-13. In addition, RANK mRNA and RANK protein were decreased by IL-4 and IL-13 in RAW 264.7 cells. Osteoblasts, spleen cells, and BMM expressed mRNA for the four proteins making up the IL-4 and IL-13 receptors. No effects by IL-4 on bone resorption and osteoclast formation or on RANKL and RANK mRNA expression were seen in Stat6-/- mice. The data indicate that IL-4 and IL-13, via a STAT6-dependent pathway, inhibit osteoclast differentiation and bone resorption by activating receptors on osteoblasts and osteoclasts that affect the RANKL/RANK/OPG system.

Animals↗
PubMed1986

Parathyroid hormone-like effects of rainbow trout Stannius products on bone resorption of embryonic mouse calvaria in vitro.

Products of the Stannius corpuscles (SC) of rainbow trout were tested in an established PTH bioassay involving bone resorption in embryonic mouse calvaria. Aqueous extracts from Stannius corpuscles (SC-homogenate) showed a bone-resorbing activity comparable to PTH in 24-h cultures of calvaria, indicated by a dose-dependent stimulation of lactate production and of calcium, phosphate as well as beta-glucuronidase release. Moreover, SC-homogenates induced an increase in osteoclastic activity. The PTH-like SC-principle is released during in vitro incubations of the glands. These results and the lack of an additive effect of SC-products and PTH on bone resorption suggest that both products activate the same receptor. We hypothesize that the hypocalcemic hormone of the SC of fish shares structural resemblance with PTH, the major hypercalcemic hormone of terrestrial vertebrates.

Animals↗
PubMed1996

Pharmacologic inhibition of particulate-induced bone resorption.

In this study, a rat calvaria/macrophage co-culture model was used to study the effects of various agents upon bone resorption induced by macrophage exposure to bone cement particles. The experimental group consisted of calvaria bone disks set in tissue culture medium on stainless-steel platforms into wells with macrophages adherent to the bottom which are exposed to the particles. Tumor necrosis factor alpha (TNF-alpha), prostaglandin E2 (PGE2), and calcium 45 (Ca45 were released in significant amounts in this system. Interleukin 1 alpha (IL-1 alpha) was not detected. Indomethacin inhibited the production of PGE2, but did not affect TNF release or inhibit the release of Ca45. Anti-TNF antibody neutralized the presence of TNF to undetectable levels, but did not affect PGE2 release or inhibit Ca45 release. The addition of calcitonin did not inhibit Ca45 release by calvaria. In contrast, the addition of disodium pamidronate, a member of the bisphosphonate family, was effective in inhibiting the release of Ca45 even after 96 h of incubation. In prior studies, incubation of calvaria in conditioned medium from macrophages exposed to cement particles led to resorption through a mechanism which is dependent upon TNF production by macrophages, and PGE2 production by cells in bone. In this two-way system, in which macrophages and cells in bone are allowed to interact, this dependency was no longer evident. Pamidronate was the only agent tested which suppressed the increase in bone resorption associated with macrophage exposure to bone cement particles to levels which were not significantly different from unexposed calvaria. By delaying or preventing bone resorption associated with macrophage exposure to bone cement particles, bisphosphonates may have a clinical role in cemented joint arthroplasty by decreasing the rate or incidence of aseptic loosening and prolonging implant longevity.

Analysis of Variance↗