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Results for “Bone Resorption”

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PubMed1998

Prognostic value of the serum levels of bone formation and bone resorption markers in prostate cancer patients with bone metastasis.

OBJECTIVE: The aim of the present study was to determine whether the serum levels of a bone formation marker, i.e., the carboxy-terminal propeptide of type I procollagen (PICP), and a bone resorption marker, i.e., the carboxy-terminal telopeptide of type I collagen (ICTP) have prognostic value in prostate cancer patients with bone metastasis, compared with alkaline phosphatase (ALP) and prostate-specific antigen (PSA). METHODS: The serum levels of PICP, ALP, ICTP and PSA were examined in 116 untreated prostate cancer patients (40 patients with bone metastasis, 76 patients without bone metastasis), and the prognoses of the patients with bone metastasis were evaluated using univariate and multivariate analyses. RESULTS: The bone metastasis patients with low PICP or ALP values had significantly better outcomes compared to the bone metastasis patients with high PICP or ALP values. A multivariate analysis of PICP, ICTP, ALP, PSA and the patients' age revealed that PICP and patients' age were important prognostic factors for survival. The pretreatment levels of ICTP and PSA did not show any substantial relation to the prognosis of these patients. CONCLUSIONS: The results suggest that the pretreatment serum bone formation marker is an important prognostic indicator for prostate cancer patients with bone metastasis.

Aged↗

PubMed1993

High-dose gestagens modulate bone resorption and formation and enhance estrogen-induced endosteal bone formation in the ovariectomized mouse.

To determine if gestagens of two separate classes have differing skeletal actions, we studied the effects of pharmacologic doses of norethisterone acetate (NETA), a 19-nortestosterone, and megestrol acetate (MA), a 17 alpha-hydroxyprogesterone, on bone formation and resorption in intact and in ovariectomized mice. In the same set of experiments, we also attempted to determine if these gestagens can alter the skeletal activity of 17 beta-estradiol (E2). Experimentally, the skeletons of 78 female BALB/c mice were prelabeled with [3H]tetracycline (3H-T). The animals were randomized to 13 groups of 6 mice each 3 days after the final 3H-T injection. Ovariectomies (OVX) were performed on 8 groups and sham operations (SO) on 5 groups. To study the skeletal effects of the gestagens, 4 groups each of the OVX and SO mice were treated with controlled-release pellet implants calculated to deliver 80 or 250 micrograms of NETA or MA per day. To study gestagen interactions with E2, 3 groups of OVX mice were treated with either 40 micrograms/day of E2 or 40 micrograms/day of E2 plus 250 micrograms/day of NETA or MA. One group of OVX and one group of SO animals received placebo pellets. Fluorochrome labels were administered 10 and 11 and 3 and 4 days before sacrifice to allow histomorphometric evaluation of bone formation. At the end of the 60 day protocol, tibiae and thoracic vertebrae were removed and processed for quantitating the levels of bone resorption based on the amounts of 3H-T retained in the bones. The femora were fixed and embedded for comparison of diaphyseal bone histomorphometry, and the humeri and lumbar vertebrae were prepared for bone density determinations. Reflecting an increase in bone resorption, 3H-T levels in tibiae and vertebrae were decreased in placebo-treated OVX animals compared to the placebo-treated SO group (p < 0.01). Treatment of both SO and OVX mice with NETA decreased bone resorption in a dose-dependent manner, but MA had no significant effects on vertebral bone resorption and increased bone resorption in the tibiae (p < 0.01). E2 treatment of OVX mice reduced bone resorption, but there were no significant interactions between the E2 and gestagen treatments on resorptive activity. Based on bone histomorphometry of in vivo fluorochrome labels, both gestagens increased periosteal bone formation rates but had no effect on endosteal bone formation (BFRe). In contrast, E2 treatment of the OVX mice stimulated bone formation at the endosteal surface.(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of Variance↗

PubMed1980

Effects of a bone resorptive factor from human cancer ascites fluid on rat bone cell calcium and cyclic AMP.

The effects of a bone resorptive protein isolated from human cancer ascites fluid on bone cell calcium and cyclic AMP were studied with fetal rat cells. The osteoclast-activating factor increased bone cell calcium uptake at 37 degrees C and 4 degrees C with no direct effects on calcium efflux. Concentrations of the resorptive factor that increased in vitro bone resorption and cell calcium uptake had no effect on cyclic AMP. The effects of the protein on calcium uptake were not specific for bone cells, and large increases were also observed in isolated fetal rat skin cells. These studies suggest that increases in the permeability of the cell membrane to calcium are involved in the mechanism of action of the ascites fluid resorptive protein.

Animals↗

PubMed1993

Role of cytokines in the regulation of bone resorption.

The process of bone remodeling involves complex interactions between the osteoclast, the primary bone-resorbing cell, and other cells in its microenvironment. These interactions can regulate bone resorption through two processes: (1) effects on the number of osteoclasts present at a given site and (2) effects on the bone-resorbing capacity of individual osteoclasts. Cells present in the osteoclast microenvironment include marrow stromal cells, osteoblasts, macrophages, T-lymphocytes, and marrow cells. These cells, as well as the osteoclast itself, produce cytokines that can affect osteoclast formation and osteoclast activity. In vitro model systems using rodent organ cultures or long-term marrow culture systems, and in vivo models have demonstrated that cytokines such as interleukin-1, M-CSF, tumor necrosis factor, and interleukin-6 can stimulate the formation and bone-resorbing capacity of osteoclasts. In contrast, cytokines such as interleukin-4, gamma-interferon, and transforming factor-beta inhibit both osteoclast formation and osteoclast activity. The relative proportions of these cytokines in the marrow microenvironment may play a critical role in regulating osteoclast activity. Knowledge of cytokines that affect osteoclast formation and activity and their capacity to modulate the bone-resorbing process should provide critical insights into normal calcium homeostasis and disorders of bone turnover such as osteoporosis and Paget's disease of bone.

Animals↗

PubMed1992

Stimulation of bone resorption results in a selective increase in the growth rate of spontaneously metastatic Walker 256 cancer cells in bone.

To test the hypothesis that bone metastasis is related to the rate of bone remodeling, we have examined the effect of enhanced bone resorption on the growth of spontaneously metastatic Walker 256 (W256) cancer cells. Bone resorption was stimulated in male Fischer rats by injecting Rice H-500 Leydig tumor cells subcutaneously. The resorptive response of the skeleton was confirmed in a pilot study by evaluating parameters of bone morphometry after 4, 7 and 10 days of tumor burden. The distal femoral epiphyses had 35 +/- 10% more osteoclast surface, 83 +/- 11% less osteoblast surface, and 46 +/- 5% less trabecular bone after 10 days of tumor burden, compared to non-tumor-bearing controls. To evaluate the effect of Leydig tumor-induced bone resorption on the growth response of W256 cells, 20 rats were injected intramuscularly with 2 x 10(7) W256 cells, and 20 rats were vehicle-injected. Two days later, 10 rats from each group were injected subcutaneously with Leydig tumor cells. Twelve days after W256/vehicle injection, rats were injected with [3H]thymidine, killed 2 h later, and their femurs, liver, lungs and kidneys were processed for histology. In rats injected with Leydig tumor cells only, enhanced bone resorption was confirmed by a 40 +/- 4% increase in serum calcium concentration, a 48 +/- 8% decrease in trabecular bone content, and a 72 +/- 15% decrease in osteoblast surface, compared with non-tumor-bearing rats. Metastatic W256 cells adjacent to trabecular bone in Leydig tumor-bearing rats had a 56 +/- 18% greater relative [3H]thymidine labeling index (TdR) than did W256 cells in the bones of non-Leydig tumor-bearing rats. The TdRs of W256 cells in the liver, lungs, and kidneys were not affected by Leydig tumor burden. In this model, enhanced bone resorption was associated with the selective growth promotion of metastatic W256 cells in bone, suggesting the existence of a bone-derived factor which is mitogenic to W256 cells.

Animals↗

PubMed1998

Threshold for bone resorption induced by continuous and intermittent pressure in the rat hard palate.

Osteoclastic bone resorption under the denture base has been considered to be influenced by mechanical force exerted through the denture base. However, no scientific evidence has been shown concerning whether osteoclastic bone resorption is a pressure-threshold-regulated phenomenon or merely a proportionally pressure-dependent phenomenon. In this study, a clear statistical criterion as an objective standard for the evaluation of histopathological bone resorption was established, and the relationship between the amount of continuous or intermittent compressive pressure exerted on the rat hard palate and induced osteoclastic bone resorption was studied based on this criterion. Eighty-five male rats of the Wistar strain, 15 weeks of age, were fitted with experimental dentures which were designed to exert a defined amount of continuous or intermittent compressive pressure on the intermolar region of the hard palate. No bone resorption was observed when continuous compressive pressure was < or = 1.96 kPa or when intermittent compressive pressure was < or = 9.8 kPa. In contrast, continuous compressive pressure > or = 6.86 kPa or intermittent compressive pressure > or = 19.6 kPa caused significant bone resorption in all rats studied. From these results, it was revealed that osteoclastic bone resorption under the denture base was a pressure-threshold-regulated phenomenon, and that the thresholds exist for the induction of bone resorption under the denture base by both continuous and intermittent compressive pressure, respectively. It was also clearly revealed from the results that the threshold for continuous compressive pressure is lower than that for intermittent compressive pressure.

Animals↗

PubMed1992

Tri-iodothyronine stimulates rat osteoclastic bone resorption by an indirect effect.

Tri-iodothyronine (T3) increases bone resorption in vivo and in vitro. In order to understand further the mechanisms by which this occurs we studied the effects of T3 at concentrations in the range of 1 pmol/l-1 mumol/l on bone resorption by osteoclasts isolated from neonatal rat long bones. Osteoclasts were disaggregated and incubated either with or without UMR 106 cells or with mixed bone cells. We found that there was no effect of T3 on bone resorption by osteoclasts incubated alone or co-cultured with UMR 106 cells. However, in culture with mixed bone cells there was a significant relationship between the concentration of T3 and bone resorption (r = 0.54, P = 0.01). The greatest effect was observed at a T3 concentration of 1 mumol/l at which a 1.8-fold increase in resorption was seen compared with control (P less than 0.005; paired t-test). We conclude that the ability of T3 to increase osteoclastic bone resorption is not due to a direct action of T3 on osteoclasts but is mediated by another cell present in bone. The observation that UMR 106 cells are unable to mediate this effect suggests that either the mediating cell is not osteoblastic or the phenotype of UMR 106 does not conform to the phenotype of osteoblastic cells that mediate the T3 responsiveness of bone.

Animals↗

PubMed2006

First-line therapy with thalidomide, dexamethasone and zoledronic acid decreases bone resorption markers in patients with multiple myeloma.

BACKGROUND: Bone involvement is frequently observed in multiple myeloma (MM) patients both at diagnosis and during the course of the disease. The evaluation of biochemical markers of bone turnover could allow a dynamic evaluation of the effects of a given therapy on bone metabolism. METHODS: In the present study, markers of bone resorption [urinary free pyridinoline (PYD), deoxypyridinoline (DPYD), N-terminal telopeptide of collagen I (NTX) and C-terminal telopeptide (serum crosslaps)] and of bone formation [bone alkaline phosphatase (BAP) and osteocalcin] were evaluated at diagnosis and after induction therapy in 40 patients (23M, 17F, median age = 53.5 yr) enrolled in the 'Bologna 2002' clinical trial. By study design, all patients received 4 months of combined thalidomide (100 mg/d for 2 wk then 200 mg/d), dexamethasone (40 mg/d on days 1-4, 9-12, 17-20/28 on odd cycles and on days 1-4 on even cycles) and zoledronic acid (4 mg/28 d). RESULTS: At diagnosis, although bone resorption markers were increased in more than 40% of the patients, only NTX (P = 0.029) and crosslaps (P = 0.000) were significantly related to the extent of skeletal lesions, as assessed by X-ray. After 4 months of therapy, a significant decrease in mean (+/-SE) urinary NTX (52.7 +/-6.9 nmol/mmol creatinine +/-6.9 vs. 14 +/- 1.42 nmol/mmol creatinine, P = 0.000) and serum crosslaps (6242.4 +/-945 pmol/L vs. 1414.9 +/- 173.8 pmol/L, P = 0.000) was observed in patients obtaining > or =partial response, at variance to what has been detected in patients showing <partial response. CONCLUSIONS: Among all bone resorption markers, urinary NTX and serum crosslaps seem to be strictly related to the extent of bone involvement in MM. Combined thalidomide + dexamethasone and zoledronic acid seem to be highly effective in reducing bone resorption in sensitive patients, although the relative contribution of each drug cannot yet be determined.

Adult↗

PubMed1989

Finite element method simulation of bone resorption beneath a complete denture.

Bone resorption beneath a maxillary complete denture was simulated by the finite element method, assuming that a threshold of compressive strain exists in the alveolar bone above which the resorption occurred. The pattern of predicted resorption was observed when 100 N of force was applied to three positions occlusally, and 20 N was applied facially. Moreover, we observed the effect of rebasing the denture after initial resorption. The results indicate that resorption was initiated on the facial and occlusal surfaces of the alveolar ridge and proceeded palatally. The resorption was greater as the occlusal load point moved facially and when the force was applied in the facial direction. When the load point was toward the facial, rebasing the denture accentuated the resorption, but when the load point was toward the palatal, the resorption was almost the same regardless of rebase. The pattern of simulated bone resorption was similar to that reported from clinical observations, which suggests that the resorption may be associated with compressive strains developed in the alveolar bone. The results argue for the importance of occlusal adjustment of dentures to move the occlusal load point palatally and produce balanced occlusion in protrusion and lateral excursions, especially after a rebase procedure.

Alveolar Process↗

PubMed1998

Bone resorption induced by A23187 is abolished by indomethacin: implications for second messenger utilised by parathyroid hormone.

Parathyroid hormone acts on the osteoblast to induce osteoclastic bone resorption. Parathyroid hormone utilises cyclic AMP as a second messenger in osteoblasts, but may also cause an increase in cytoplasmatic free calcium ions ([Ca2+]i) in the same cell. To investigate the role of osteoblastic [Ca2+]i in the induction of bone resorption, we have compared the effects of parathyroid hormone and the Ca2+-ionophore, A23187, as well as the adenylate cyclase stimulating agent, forskolin, and the phorbol ester, phorbole 12,13 dibutyrate (PDB), on bone resorption in neonatal mouse calvarial bones. Parathyroid hormone (0.1 and 1 nM) dose dependently stimulated the release of prelabelled 45Ca2+ in 72 h culture. Parathyroid hormone-induced bone resorption was not affected by the addition of 1 microM indomethacin to the incubation media, and was therefore, not mediated by local prostaglandin formation. A23187 stimulated the release of 45Ca2+ at 1-10 nM. Above 100 nM, A23187 inhibited bone resorption. The A23187 (3 and 10 nM)-induced bone resorption was abolished by the cyclooxygenase inhibitor, indomethacin (1 microM), indicating that the stimulatory effect was mediated via prostaglandin formation. The adenylate cyclase stimulating agent, forskolin, dose dependently stimulated bone resorption at and above 1 microM. There was no additive or synergistic effect of forskolin and A23187 on 45Ca2+ release. Forskolin-induced bone resorption was, as with parathyroid hormone but in contrast to ionophore-induced bone resorption, not abolished by indomethacin (1 microM). The protein kinase C activator, PDB, at 10 and 1000 nM stimulated the release of prelabelled 45Ca2+. The stimulatory effect of the protein kinase C stimulating phorbol ester, PDB, on bone resorption was abolished by the addition of indomethacin. In summary, bone resorption induced by a Ca2+-ionophore is abolished by indomethacin. This indicates that bone resorbing agents known to increase [Ca2+]i subsequently enhance local prostaglandin formation. Bone resorption induced by the protein kinase C activator, PDB, was also abolished by indomethacin, whereas, forskolin and parathyroid hormone-induced bone resorption was unaffected. These data indicate that cyclic AMP, but not [Ca2+]i, is involved as a second messenger in parathyroid-induced bone resorption.

Animals↗

PubMed1990

Prolonged and ubiquitous inhibition by interferon gamma of bone resorption induced by parathyroid hormone-related protein, 1,25-dihydroxyvitamin D3, and interleukin 1 in fetal mouse forearm bones.

To investigate the mechanism of the inhibitory effects of interferon-gamma (IFN-gamma) on bone resorption, the effects of murine IFN-gamma on 45Ca release from prelabeled fetal mouse forearm bones were investigated. Murine IFN-gamma usually did not affect basal 45Ca release but almost completely and equipotently inhibited bone resorption induced by PTH(1-34), PTH-rP(1-34), 1,25(OH)2D3, and interleukin 1 (IL-1). The half-maximal concentration for inhibition of bone resorption induced by IL-1 alpha was 25.8 +/- 14.6 U/ml (mean +/- SD for 13 experiments), which is not different from those for PTH, PTH-rP, and 1,25(OH)2D3. There was no correlation between prostaglandin E2 concentration in the conditioned medium and 45Ca release from the IFN-gamma-treated forearm bones. The inhibitory effect of IFN-gamma on bone resorption induced by PTH-rP (1-34) or IL-1 alpha continued during 6 days of culture, whereas that of calcitonin disappeared after 2 days of culture. These findings suggest that IFN-gamma non-preferentially inhibits bone resorption induced by various bone-resorbing factors in fetal mouse forearm bones via a PGE2-independent mechanism. As no escape phenomenon developed in IFN-gamma-treated bones, the cytokine may be potentially useful for treatment of certain patients with malignancy-associated hypercalcemia.

Animals↗

PubMed2006

B cells play an important role in lipopolysaccharide-induced bone resorption.

The host immune system, especially activated T cells, plays a crucial role in inflammatory bone resorption and osteoclastogenesis. Previously, we showed that T cells are involved in inflammatory bone resorption in vivo. However, little is known about whether B cells are involved in inflammatory bone resorption and how B cells take part in osteoclastogenesis. Therefore, the aim of this study was to examine whether B c ells truly influence inflammatory bone resorption in vivo. Alveolar bone resorption in normal mice, in SCID mice that lack both B and T cells, and in B cell-reconstituted SCID mice was compared histopathologically after repeated injections of lipopolysaccharide (LPS) into the gingiva. Furthermore, we examined whether the B cells that are stimulated by LPS are involved in osteoclastogenesis in vitro. As a result, the B cell-reconstituted SCID mice showed stronger inflammatory bone resorption than the SCID mice. Also, in vitro, LPS-stimulated B cells enhanced osteoclastogenesis and anti-tumor necrosis factor (TNF)-alpha antibody completely blocked osteoclastogenesis induced by LPS-stimulated B cells. These results suggest that B cells promote inflammatory bone resorption through TNF-alpha.

Animals↗

PubMed1982

Ultrastructural evaluation of biochemical events of bone resorption in human chronic otitis media.

Bone resorption is a significant component of chronic inflammatory ear disease. Bone is a unique tissue requiring both demineralization and collagen degradation for breakdown. Mineral removal probably occurs prior to collagen destruction. A localized change in pH may be one of the mechanisms that induces demineralization. Localized accumulations of lysosomal acid hydrolases could provide the acidic environment necessary for mineral removal. The present study utilizes the electron microscope to localize the lysosomal enzyme acid phosphatase in specimens removed from patients with chronic otitis media. Areas of localized bone resorption exhibited mononuclear inflammatory cells attached to the resorption margin. These cells contained abundant acid phosphatase, as did isolated fibroblasts within the zone of inflammation at the resorption margin. Extra cellular acid phosphatase was seen in these areas. Within the bone, osteocytes adjacent to resorption displayed increased cytoplasmic organelle patterns and contained the acid phosphatase reaction. The localization of destructive enzymes in mononuclear inflammatory cells and osteocytes explains the bony destructive changes observed in human chronic otitis media in the absence of multinucleated osteoclasts.

Acid Phosphatase↗

PubMed1992

Stimulation of osteoclastic bone resorption by hydrogen peroxide.

The molecular mechanisms underlying the pathophysiology of bone destruction still remain poorly understood. We have found that hydrogen peroxide (H2O2), a reactive oxygen species (ROS), is a potent stimulator of osteoclastic bone resorption and cell motility. A marked enhancement of bone resorption was noted when rat osteoclasts, cultured on devitalised bovine cortical bone, were exposed to 10 nM [H2O2]. Apart from exposing osteoclasts to a low extracellular pH, which is known to enhance osteoclastic bone resorption, we provide first evidence for a molecule that stimulates osteoclastic bone resorption in osteoclast cultures that do not respond to parathyroid hormone and 1, 25 dihydroxyvitamin D3. We envisage that both basic biological and practical clinical implications may eventually follow from these studies.

Animals↗

PubMed1999

Increase in the potential of osteoblasts to support bone resorption by osteoclasts in vitro in response to roughness of bone surface.

The development of the potential of osteoblasts to support bone resorption by osteoclasts in response to roughness on bone slices was examined in the co-incubation cell system of immature osteoclasts and osteoblastic cells. The immature osteoclasts, which need alkaline phosphatase (ALP)-positive osteoblastic cells for bone resorption, were generated in mouse spleen cultures with 1, 25-dihydroxyvitamin D(3) and prostaglandin E(2). ALP-negative osteoblastic cells from mouse calvaria were incubated on rough surfaced bone slices for 3 days. The number of ALP-positive cells increased greatly on the rough surface, but little on the smooth surface. When immature osteoclasts were added and incubated for 1 more day, the resorption pit number and the total pit areas on the smooth surface were not much different from those before incubation but were approximately four times higher on the rough surface.

Alkaline Phosphatase↗

PubMed2000

Tamoxifen inhibits phorbol ester stimulated osteoclastic bone resorption: an effect mediated by calmodulin.

Tamoxifen inhibits bone resorption by disrupting calmodulin-dependent processes. Since tamoxifen inhibits protein kinase C in other cells, we compared the effects of tamoxifen and the phorbol ester, phorbol myristate acetate, on osteoclast activity. Phorbol esters stimulate bone resorption and calmodulin levels four-fold (k0.5 = 0.1-0.3 microM). In contrast, tamoxifen inhibited osteoclast activity approximately 60% with an IC50 of 1.5 microM, had no apparent effect on protein kinase C activity in whole-cell lysates, and reduced protein kinase C alpha recovered by immunoprecipitation 75%. Phorbol esters stimulated resorption in a time-dependent manner that was closely correlated with a similar-fold increase in calmodulin. Protein kinase C alpha, beta, delta, epsilon, and zeta were all down-regulated in response to phorbol ester treatment. Tamoxifen and trifluoperazine inhibited PMA-dependent increases in bone resorption and calmodulin by 85 +/- 10%. Down-regulation of protein kinase C isoforms by phorbol esters suggests that the observed increases in bone resorption and calmodulin levels are most likely due to a mechanism independent of protein kinase C and dependent on calmodulin. In conclusion, the data suggest that protein kinase C negatively regulates calmodulin expression and support the hypothesis that the effects of both phorbol esters and tamoxifen on osteoclast activity is mediated by calmodulin.

Animals↗

PubMed2002

Bone-resorptive effects of endotoxin-contaminated high-density polyethylene particles spontaneously eliminated in vivo.

Wear particles commonly used for experiments may carry adherent endotoxin on their surfaces, which may be responsible for the observed effects. In this study, we attached titanium plates to the tibiae of 20 rats. After osseointegration, endotoxin-contaminated or uncontaminated high-density-polyethylene (HDPE) particles were applied. Contaminated specimens showed a dramatic resorption of bone after seven days but new bone filled the site again at 21 days. Uncontaminated specimens showed no resorption. In 18 rats we implanted intramuscularly discs of ultra-high-molecular-weight polyethylene (UHMWPE) with baseline or excess contamination of endotoxin. Excess endotoxin disappeared within 24 hours and the amount of endotoxin remained at baseline level (contamination from production). Uncontaminated titanium discs did not adsorb endotoxin in vivo. The endotoxin was measured by analytical chemistry. Locally-applied endotoxin stimulated bone resorption similarly to that in experiments with wear particles. Endotoxin on the surface of implants and particles appeared to be inactivated in situ. A clean implant surface did not adsorb endotoxin. Our results suggest that endotoxin adhering to orthopaedic implants is not a major cause for concern.

Animals↗

PubMed1986

Preferential inhibition of cytokine-stimulated bone resorption by recombinant interferon gamma.

It is likely that immune cells in the bone marrow produce factors which are involved in the local control of bone remodeling. Immune cell products such as interleukin-1 and the tumor necrosis factors are potent stimulators of bone resorption in vitro. In this paper, we have studied the effects of recombinant murine interferon-gamma on bone resorption stimulated by these agents and the systemic calcium-regulating hormones 1,25(OH)2 vitamin D3 and parathyroid hormone. We found that interferon-gamma completely abolished bone resorption stimulated by the cytokines interleukin-1, tumor necrosis factor alpha and tumor necrosis factor beta. In contrast, parathyroid hormone- and 1,25(OH)2 vitamin D3-stimulated bone resorption were not significantly affected by the addition of interferon-gamma under the same conditions. Parathyroid hormone-stimulated bone resorption was inhibited slightly when larger concentrations of interferon-gamma were used for more prolonged periods. The inhibitory effects on cytokine-stimulated bone resorption occurred at interferon concentrations of 100 U/ml (half-maximal) to 300 U/ml (complete inhibition). This relatively selective inhibition of cytokine-stimulated bone resorption by an immune cell product may have physiological significance in the local control of trabecular bone volume and bone remodeling.

Animals↗