[Intracortical bone resorption: its diagnostic value in metabolic bone diseases associated with high bone-turnover].
Explore the source record for details and available documents.
Bone Diseases, Metabolic↗
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.
Inhibitory activity of Drynariae rhizoma extracts on cathepsin having bone resorption activity.
Effects of traditional Korean (Hanbang) medicine, Drynariae rhizoma (DR), on the protease activity of bone loss-initiation in rats and mice were investigated. Ethanol extracts-DR (EE-DR) and water extracts-DR (WE-DR) were identified as potent inhibitor of cathepsins K and L. The original WE-DR inhibits cathepsins K and L with IC50 values of 3.7 microg/ml and 4.5 microg/ml, respectively. EE-DR was more potent than that of WE-DR, because the inhibitions of cathepsin K and L increased to 0.5 microg/ml and 0.8 microg/ml, respectively. The EE-DR was proved to be the most potent. EE-DR was found to be a potent inhibitor of cathepsins K with a Ki value of 5.0 microg/ml for cathepsin K. The activity was increased by 10-fold when the assay is performed in the presence of glutathione at pH 7.0, which favors the formation of a GSH thiolate anion. Thus, it is suggested that this increase in potency is probably due to an enhanced chemical reactivity of the extract mixtures toward the thiolate of the active site of the enzyme. WE-DR exhibited time-dependet inhibition which allowed us to determine the association and dissociation rate constants with cathepsin K. Finally, EE-DR inhibits bone resorption in an in vitro assay involving mouse osteoclasts and bovine bone with an IC50 value of 70 microg/ml. WE-DR represents a new herbal formulation inhibiting cathepsin K and L activity and proteolysis of bone collagen. These results strongly suggest that DR is effective for preventing the development of bone loss induced by cathepsin K. This result also suggested that the DR is effective for bone resorptive action in bone cells.
Animals↗
Increased bone resorption in moderate smokers with low body weight: the Minos study.
Tobacco was found to be a risk factor for osteoporosis, mainly in postmenopausal women. We studied the effect of smoking on bone mineral density (BMD) and bone turnover in a cohort of 719 men, aged 51-85 yr, composed of 83 current smokers, 405 former smokers, and 231 men who never smoked. Most current and former smokers were moderate smokers (median, 10 cigarettes/d). Current smokers were younger, thinner, and drank more coffee and more alcoholic beverages. After adjustment for age, body weight, alcohol intake, and caffeine intake, current and former smokers had similar BMD, except at the forearm. Former smokers had lower BMD compared with never-smokers at most skeletal sites. Men who had smoked more than 7120 packs (third quartile) had lower BMD of total hip (P < 0.01) and distal forearm (P = 0.03) compared with men in the 2 lower tertiles. In the 3 groups, levels of bone formation markers did not differ. After adjustment for confounding variables, levels of urinary markers of bone resorption (beta-isomerized C-terminal telopeptide, free and total deoxypyridinoline) were higher in the current smokers than in former smokers and never-smokers. Concentrations of T, total 17beta-E2, and androstenedione were higher, whereas that of 25-hydroxyvitamin D was lower, in current smokers. When men were divided according to tertiles of body weight, increased bone resorption, decreased BMD and biochemical indexes of secondary hyperparathyroidism were observed in current smokers in the lowest tertile of body weight (<75 kg) compared with the never-smokers, but not in men in the two highest tertiles of body weight. Current smokers had a higher prevalence of vertebral deformities after adjustment for age and body weight (13% vs. 5%; P < 0.005). In summary, in moderate smokers with low body weight (<75 kg), increased bone resorption, not matched by increased bone formation, results in decreased BMD and an increased prevalence of vertebral deformities. In this group, low serum 25-hydroxyvitamin D and secondary hyperparathyroidism may explain, at least partly, the effect of tobacco on bone turnover. In former smokers, bone resorption is not increased, but BMD remains lower compared with that in never-smokers.
Aged↗
Bilateral tibial marrow ablation in rats induces a rapid hypercalcemia arising from extratibial bone resorption inhibitable by methylprednisolone or deflazacort.
The goals of this study were to quantitate biochemical markers of bone metabolism on days 1-15 after bilateral tibial marrow ablation surgery in young adult rats and to determine the effect of a single dose of methylprednisolone (2 mg/kg) or deflazacort (2.5 mg/kg) given at the time of ablation. Unexpectedly, serum calcium levels rose to a maximum of 15.9 mg/dl on day 7 after marrow ablation and remained above normal through day 15. This increase was blocked by a single intramedullary injection of methylprednisolone or deflazacort immediately following ablation; however, the fact that both drugs produced a characteristic rapid 3- to 10-fold increase in the serum alpha 2-macroglobulin level demonstrates that the drugs rapidly reached the circulation. Both methylprednisolone and deflazacort also inhibited intramedullary deposition of collagen by 40-60% on day 7, a time near which operated control animals achieved maximal accumulation of new bone in this model. Histological comparisons among the three experimental groups were largely consistent with biochemical results. The urinary hydroxyproline/creatine ratio for the operated control group doubled on day 3 and then returned to presurgical levels on day 7 and later. The timing and size of the hydroxyproline/creatinine peak, as well as the fact that the intratibial osteoclastic response peaks on days 8-10 after ablation, suggests it results from extratibial bone resorption induced by marrow ablation. Consistent with this rationale, urinary calcium excretion in operated controls rose 9-fold from day 0 to day 3 and appeared to plateau over the period from day 3 to day 9, before returning to a near presurgical level on day 15. Elevated excretion of calcium noted on days 9-15 in deflazacort-treated animals, which occurs in the absence of a detectable increase in resorption marker hydroxyproline, may however be due to the known action of glucocorticoids in increasing kidney filtration of calcium. In summary, this is the first report to show that bilateral tibial marrow ablation in rats causes a rapid hypercalcemia and calciuria which is accompanied initially by a peak of bone resorption marker urinary hydroxyproline. We speculate that the source of calcium and hydroxyproline is extratibial osteoclastic bone resorption induced by circulating cytokines whose release from ablated tibias or osteoclastogenic action is inhibitable by methylprednisolone and deflazacort.
Animals↗
Cortisol inhibits acid-induced bone resorption in vitro.
Metabolic acidosis increases urine calcium excretion without an increase in intestinal calcium absorption, resulting in a net loss of bone mineral. In vitro, metabolic acidosis has been shown to initially induce physicochemical mineral dissolution and then enhance cell-mediated bone resorption. Acidic medium stimulates osteoblastic prostaglandin E(2) production, which mediates the subsequent stimulation of osteoclastic bone resorption. Glucocorticoids are also known to decrease bone mineral density, and metabolic acidosis has been shown to increase glucocorticoid production. This study tested the hypothesis that glucocorticoids would exacerbate acid-induced net calcium efflux from bone. Neonatal mouse calvariae were cultured in acid (Acid; pH = 7.06 +/- 0.01; [HCO(3)(-)] = 10.6 +/- 0.3 mM) or neutral (Ntl; pH = 7.43 +/- 0.01; [HCO(3)(-)] = 26.2 +/- 0.5 mM) medium, with or without 1 microM cortisol (Cort), and net calcium efflux and medium prostaglandin E(2) (PGE(2)) levels and osteoclastic beta-glucuronidase activity were determined. Compared with Ntl, Cort alone decreased calcium efflux, medium PGE(2), and osteoclast activity; Acid led to an increase in all three parameters. The addition of Cort to Acid led to a reduction of calcium efflux, medium PGE(2) levels and beta-glucuronidase activity compared with Acid alone. There was a significant direct correlation between medium PGE(2) concentration and net calcium efflux (r = 0.944; n = 23; P < 0.0001), between osteoclastic beta-glucuronidase activity and net calcium efflux (r = 0.663; n = 40; P < 0.001), and between medium PGE(2) concentration and beta-glucuronidase activity (r = 0.976; n = 4; P < 0.01). Thus, in vitro cortisol inhibits acid-induced, cell-mediated osteoclastic bone resorption through a decrease in osteoblastic PGE(2) production. These results suggest that the osteopenia observed in response to metabolic acidosis in vivo is not due to an increase in endogenous cortisol production.
Acids↗
Endothelin-1 from prostate cancer cells is enhanced by bone contact which blocks osteoclastic bone resorption.
The causes for the propensity of metastasized prostate cancer cells to grow in bone and to induce osteoblastic lesions remain unresolved. Co-culture of human prostate cancer cell lines with bone slices was determined to increase the level of endothelin-1 (ET-1) mRNA and its production. ET-1 is an ejaculate protein that also stimulates osteoblasts. Osteoclastic bone resorption was significantly blocked by the presence of androgen-independent prostate cancer cells in a dose-dependent manner as that of synthetic ET-1. The inhibition could be neutralized by specific ET-1 antibody, indicating the association of prostate cancer-derived ET-1 with inhibition of bone resorption. The combined ET-1 activity on osteoclasts and osteoblasts disrupts bone remodelling. ET-1 production is also elevated in the presence of prostate-specific antigen (PSA). ET-1 in turn enhances DNA synthesis of prostate cancer cells. Interactions among cancer cells, bone, ET-1 and PSA may be critical in cancer growth and lesions in bone.
Analysis of Variance↗
Inhibition of bone resorption in vitro and prevention of ovariectomy-induced bone loss in vivo by flurbiprofen nitroxybutylester (HCT1026).
OBJECTIVE: Inhibitors of prostaglandin production, such as nonsteroidal antiinflammatory drugs (NSAIDs), and pharmacologic nitric oxide (NO) donors, such as organic nitrates, have been suggested to protect against bone loss in both humans and experimental animals. Recently, a new class of nitrosylated NSAID (known as NO-NSAIDs) has been developed, which combines the properties of a NO donor with those of a cyclooxygenase (COX) inhibitor. This study investigated the effects of one of these compounds, flurbiprofen nitroxybutylester (HCT1026), on bone metabolism in vitro and in vivo. METHODS: The effects of HCT1026 on osteoclast formation and resorption were determined in vitro using cocultures of primary mouse osteoblasts and osteoclasts. The effect of HCT1026 in vivo was assessed using a mouse model of ovariectomy-induced bone loss. RESULTS: HCT1026 was significantly more efficacious than the parent compound, flurbiprofen, at inhibiting osteoclast formation and bone resorption in vitro, and these effects could not be reproduced by combinations of flurbiprofen with a variety of NO donors. Studies in vivo showed that HCT1026 protected against ovariectomy-induced bone loss by inhibiting osteoclastic bone resorption, whereas flurbiprofen at similar concentrations was ineffective. CONCLUSION: These data indicate that HCT1026 is a potent inhibitor of bone resorption in vitro and protects against ovariectomy-induced bone loss in vivo by a novel mechanism that appears to be distinct from its NO donor properties and from its inhibitory effects on COX activity. We conclude that HCT1026 may be of clinical value in the prevention and treatment of inflammatory diseases such as rheumatoid arthritis, which are characterized by joint inflammation as well as periarticular and systemic bone loss.
Animals↗
Porphyromonas gingivalis fimbriae stimulate bone resorption in vitro.
Our previous study demonstrated that Porphyromonas gingivalis fimbriae induce the expression of interleukin-1, a potent bone-resorbing cytokine, in macrophages. This demonstration suggested to use the possibility that the fimbriae may stimulate bone resorption via the generation of an inflammatory cytokine(s). The present study was performed to test this suggestion. The bone-resorbing activity was evaluated by measuring the area of resorption lacunae on bone slices incubated with calvarial bone cells taken from 14-day-old mouse embryos. Fimbriae at 0.5 micrograms of protein per ml stimulated the bone-resorbing activity significantly, and the effect was dose and treatment time dependent. Since it is well known that interleukin-1 and granulocyte macrophage colony-stimulating factor induce differentiation of osteoclast lineage cells, we examined the involvement of these cytokines in fimbria-stimulated bone resorption. Fimbria-stimulated bone resorption was abolished significantly by antisera against both cytokines. We observed by Northern (RNA) blot assay that both cytokine genes were markedly expressed in the fimbria-treated calvarial bone cells. Our present data demonstrate that P. gingivalis fimbriae stimulate bone resorption in vitro.
Animals↗
Glutamate receptors are expressed by bone cells and are involved in bone resorption.
The excitatory amino acid glutamate (Glu) is a potent neurotransmitter in the central nervous system and exerts its action via a variety of glutamate receptors (GluRs). Because we had previously shown that a poly-glutamate (poly-Glu) peptide stimulates bone resorption in vitro, an effect specific to Glu (Raynal, C., Delmas, P. D., and Chenu, C. Bone sialoprotein stimulates in vitro bone resorption. Endocrinology 137:2347-2354; 1996), we investigated the possibility that bone cells express GluRs, and whether they may be important for osteoclast activity. Using immunocytochemistry on rat bone sections, we have shown that all mature bone cells (osteoblasts and osteoclasts) express GluRs, and that the ionotropic N-methyl-D-aspartate (NMDA) receptor 1 subunit (NMDAR1) appears most highly expressed. Osteoclasts isolated from rabbit long bones also possessed NMDAR1 GluRs. Bone resorption in vitro by isolated osteoclasts was inhibited by a monoclonal antibody directed against NMDAR1, as well as by two pharmacological antagonists of this receptor (D-AP5 and MK 801), which also antagonized poly-Glu stimulated bone resorption. These results suggest a possible new mechanism for regulating osteoclast activity and indicate that excitatory amino acids such as glutamate may be important local regulators of bone cell functions.
2-Amino-5-phosphonovalerate↗
Vitamin D intoxication causes hypercalcaemia by increased bone resorption which responds to pamidronate.
OBJECTIVE: Vitamin D intoxication is a relatively rare but treatable cause of hypercalcaemia. In the past this has been undertaken using corticosteroids. Previous observations have suggested that there is increased bone resorption in hypervitaminosis D. If this were to be the case, specific inhibitors of bone resorption might provide more effective treatment. We have therefore studied the mechanisms of hypercalcaemia and response to therapy in a group of patients with vitamin D intoxication. DESIGN: Vitamin D metabolites were measured in six patients with vitamin D intoxication; in five of these the components of hypercalcaemia were calculated. These measurements were repeated following treatment with corticosteroids (two patients) or the bisphosphonate, pamidronate (three patients). RESULTS: In each case the serum 25-hydroxyvitamin D was grossly elevated and there was a more modest elevation in serum 1,25-dihydroxyvitamin D. The components of hypercalcaemia suggest that there was a significant degree of bone resorption in all six patients and that this is the major determinant of hypercalcaemia. Pamidronate treatment resulted in a brisk reduction in plasma calcium concentration. Following corticosteroids the return of calcium to normal was more delayed. CONCLUSION: The hypercalcaemia of vitamin D intoxication is mediated by increased bone resorption and bisphosphonates have a role in its management.
Adrenal Cortex Hormones↗
In vitro bone resorption activity produced by a hypercalcemic adenocarcinoma tumor line (CAC-8) in nude mice.
Tumor extracts and conditioned tissue culture media from a canine adenocarcinoma tumor line (CAC-8) propagated in nude mice significantly increased in vitro bone resorption in neonatal mouse calvaria as measured by release of previously incorporated 45Ca. In vitro bone resorption activity was induced in a dose-dependent manner, was not suppressible by indomethacin, and was heat- and acid-stable. Gel exclusion chromatography demonstrated peak bone resorbing activity at a relative molecular mass of approximately 28,000. The parathyroid hormone (PTH) antagonist (8,18norleucine, 34tyrosine) bovine PTH (3-34) amide did not inhibit CAC 8-stimulated or (1-34) bPTH-induced bone resorption. There was an increased number of tartrate-resistant, acid phosphatase-positive cells in calvariae exposed to CAC-8 extract. Ultrastructural evaluation of calvaria revealed hypertrophy and maturation of osteoclasts in calvaria exposed to CAC-8 extract. The maturation effects included close contact to bone surfaces and the presence of clear zones and ruffled borders in osteoclasts. Similar structures were observed infrequently in osteoclasts of control calvaria. These data demonstrate that the tumor line (CAC-8) contained activity capable of stimulating in vitro bone resorption by increasing osteoclast numbers and the activity of existing osteoclasts.
Adenocarcinoma↗
Low dose estrogen and calcium have an additive effect on bone resorption in older women.
Previous studies have shown that treatment with estrogen or calcium decreases bone turnover in older women. The mechanisms by which estrogen and calcium exert their effects are probably different. We therefore examined the possibility of an additive or synergistic effect of combined treatment with calcium and low dose estrogen on bone turnover in older women, using biochemical markers. Thirty-one healthy women over 70 yr of age were randomized to 12 weeks of treatment with either micronized 17beta-estradiol [0.5 mg/day Estrace (E2)] or 1500 mg/day elemental calcium, given as carbonate plus vitamin D (800 IU/day; Ca+D). At the end of the initial 12-week treatment period, both groups received both Ca+D and E2 for an additional 12 weeks. Eleven older women were followed for 36 weeks without any treatment and served as a control group. Serum and urine were collected at baseline, at 12 and 24 weeks on treatment, and at 12 weeks after treatment was terminated for measurement of biochemical markers of bone turnover. Markers of bone formation were bone alkaline phosphatase, osteocalcin, and type I procollagen peptide; markers of bone resorption were urinary cross-linked C-telopeptides and N-telopeptides of type I collagen, serum cross-linked N-telopeptides of type I collagen, urinary free deoxypyridinoline cross-links, and serum bone sialoprotein. Repeated measures ANOVA was used to determine changes in bone turnover measures over time by group. All markers of bone resorption decreased with initial treatment and decreased further with combination therapy (P < 0.001). Markers of bone formation decreased with Ca+D treatment, but not with E2 alone; there was no additional effect of combination therapy on formation markers compared to Ca+D alone. Neither markers of formation nor resorption changed in the control group. These results suggest that there is an additive effect of low dose estrogen and calcium on bone resorption, but not on bone formation, in older women. Thus, the combination of low dose estrogen plus calcium is likely to be more effective in older women than either treatment alone.
Aged↗
The mechanism of bone resorption by cyclosporin: involvement of the NO-cGMP pathway.
Treatment with cyclosporin A (CsA) following solid organ transplantations such as heart or liver generally results in bone loss. However, in vitro studies show that CsA inhibits bone resorption. Our previous in vivo animal studies demonstrated that the effects of nitric oxide (NO) on bone are biphasic; at high doses, NO increases bone resorption. In this study, we have examined in an in vitro setting to determine whether the bone loss caused by CsA administration is dependent on the NO-cyclic guanosine monophosphate (cGMP) pathway. Freshly isolated osteoclast-rich neonatal rat long bone marrow cells were added to 100 microM thick dentin sections that had been seeded with neonatal-rat calvarial osteoblasts. These co-cultures were maintained for 48 hrs in a basal medium with CsA (1, 5, and 10 microg/ml), both alone and with either L-Arginine (NO substrate; 10-3M), L-NAME (NO synthase enzyme inhibitor; 10-4M), or the combination of the two. The cultures were then fixed in cold 95% ethanol and stained with tartrate resistant acid phosphatase (TRAP) to identify osteoclasts and sites of osteoclastic resorption. Preparations were analyzed using an automated histomorphometry software package. Scanning electron microscopy affirmed that the areas identified by light microscopy as resorption sites contained osteoclastic lacunae. CsA inhibited bone resorption dose-dependently. CsA at 10 microg/ml produced a 90% inhibition of bone resorption (control = 5.5 -/+2.0%; CsA = 0.64 -/+ 0.09=). L-Arginine reversed this inhibition by 90% (Arg + CsA = 4.23 -/+ 1.57%; CsA = 0.64 -/+ 0.09%). The application of NOS inhibitor L-NAME inhibited bone resorption by 87% (Arg + CsA + L-NAME = 0.55 -/+ 0.14%; Arg + CsA = 4.23 -/+ 1.5%). We conclude that NO-cGMP pathway is involved in the CsA induced bone loss.
Journal Article↗
An electron microscopic observation on cells found in bone resorption area incident to experimental tooth movement.
For the purpose of investigating many of the cells in the bone resorption area incident to experimental tooth movement and characterizing the role of these cells for the periodontal tissue resorption at the ultrastructural level, orthodontic force was applied to 24 male rats. Orthodontic elastics were inserted into the interproximal space of the upper first and second molars. The mesial side of the interradicular septum of the second molar was observed. The electron micrsocopic findings were as follows: 1. Cell cohorts were found in the undermining bone resorption area. They are mainly composed of fibroblasts, endothelial cells, undifferentiated cells, macrophages and several kinds of osteoclasts. 2. Four different kinds of osteoclasts could be recognized from the morphological features: a) small osteoclasts situated apart from the bone surface, b) large osteoclasts rich in rough ER, c) classic large osteoclasts and d) degenerating osteoclasts. 3. Two different types of undifferentiated cells were observed in these area. One was a spindle-shaped bright cell rich in rough ER and the other was a round-shaped dark cell with numerous mitochondria and free ribosomes. 4. Macrophages showing phagocytosis were also found in the bone resorption area.
Animals↗
Single infusion of neridronate (6-amino-1-hydroxyhexylidene-1,1-bisphosphonate) in patients with active rheumatoid arthritis: effects on disease activity and bone resorption markers.
AIMS: The aim of this study was to assess the effects of a single infusion of the bisphosphonate neridronate (N) on parameters of inflammation and bone resorption in rheumatoid arthritis (RA). METHODS: Forty-five patients with active RA were randomly allocated on a double blind basis to receive a single intravenous infusion of either N 25 mg (15 patients), N 50 mg (15 patients), or placebo (15 patients). At baseline and after 7 and 21 days, we assessed the following: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and Ritchie's articular index as indices of disease activity; and urinary free deoxypyridinoline (DPyr), N-telopeptide of type I collagen (NTx) and hydroxyproline (OHP) as indices of bone resorption. RESULTS: At day 7, N 25 mg significantly decreased ESR compared to N 50 mg (p=0.002), and CRP compared to placebo (p=0.036). With regard to bone resorption markers, at day 7, both N 25 mg and 50 mg compared to placebo significantly decreased NTx (p<0.0005 and p=0.003, respectively) and OHP (p=0.001 and p=0.004, respectively). At day 21, N 50 mg significantly decreased OHP compared to placebo (p=0.017). DPyr levels remained unchanged in the three groups. CONCLUSIONS: N 25 mg and 50 mg exerted different effects on RA activity parameters, since only the lower dose significantly decreased ESR and CRP. Both doses of N inhibited bone resorption, with a transient, significant reduction in urinary NTx and OHP, but without any effect on DPyr.
Aged↗
Urinary bone resorption markers in monitoring treatment of symptomatic osteoporosis.
We have studied the clinical usefulness of urinary bone resorption markers in postmenopausal women with symptomatic osteoporosis. The study design is a randomised double-blind placebo controlled study, in which the subjects were daily treated for 24 months either with a hormone analogue (2.5 mg Livial, generic name Tibolone, Organon, Amsterdam, Holland) plus 800 mg calcium (n = 14, age 63+/-5 years, range 52-68 years), or with placebo plus 800 mg calcium (n = 19, age 66+/-7 years, range 50-75 years). The laboratory methods for urinary bone resorption markers were enzyme immunoassays (EIA) for urinary pyridoline (PYD) and deoxypyridoline crosslinks (DPD), and for cross-linked N-telopeptides of Type I Collagen (NTx), and an HPLC assay for urinary hydroxyproline (HOP). All the urine assay results were calculated per mmol creatinine. All the resorption markers decreased during the two-year study period in both groups. The Z scores (discriminating power, i.e. ability of the different tests to distinguish the hormone treated subjects from the placebo treated subjects) for HOP and PYD were rather low: 0.06-1.52 for HOP and 0.68-1.47 for PYD. The differences between the two treatment groups were statistically significant for DPD at 12 and 24 months of treatment (P = 0.0471 and P = 0.0466, respectively), the Z scores ranging 0.45-1.90. NTx showed the most prominent decrease from the beginning of the study especially in the hormone treatment group: the differences between the two treatment groups were statistically highly significant for NTx already at 6 months of treatment (P = 0.0015), and the Z scores remained high ranging 2.11-3.82 throughout the two-year study period. Dual X-ray absorptiometry (DXA) of the lumbar spine and femoral neck did not show statistically significant differences between the two treatment groups throughout the two-year study period. After 2 years there was, however, a significant increase in bone density both in the spine (+ 6.6%, P = 0.0002) and in the femoral neck (+ 3.4%, P = 0.0389) in the women with hormone treatment. In the control group a significant increase (+ 5.1%, P = 0.0012) in the spine, whereas a non-significant decrease (-1.5%, n.s.) in the femoral neck was observed. We suggest that measurement of urinary cross-linked peptides derived from Type I collagen (NTx and DPD) might be a useful biochemical method of observing the positive clinical effect (i.e. reduction in bone resorption) following hormone replacement therapy in postmenopausal fracture patients.
Aged↗
Effects of cholera toxin on cyclic AMP accumulation and bone resorption in cultured mouse calvaria.
We have utilized the adenylate cyclase stimulator, cholera toxin, as a tool to test the role of cyclic AMP as a mediator of the effects on bone resorption by the calcium-regulating hormones, parathyroid hormone (PTH) and calcitonin. The effects on bone resorption were studied in an organ culture system using calvarial bones from newborn mice. Cyclic AMP response was assayed in calvarial bone explants and isolated osteoblasts from neonatal mouse calvaria. Cholera toxin caused a dose-dependent cAMP response in calvarial bones, seen at and above approx. 1-3 ng/ml and calculated half-maximal stimulation (EC50) at 18 ng/ml. The stimulatory effect of cholera toxin could be potentiated by the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX, 0.2 mmol/l). Cyclic AMP accumulation in the bones was maximal after 4-6 h, and thereafter declined. However, activation of the adenylate cyclase was irreversible and the total amount (bone + medium) of cAMP produced, in the presence of IBMX (0.2 mmol/l), increased with time, for at least 48 h. In osteoblast-like cells cholera toxin (1 microgram/ml) stimulated the cellular levels of cAMP with a peak after 60-120 min, which could be potentiated with IBMX. The total cAMP accumulation indicated an irreversible response. In short-term bone organ cultures (at most, 24 h) cholera toxin, at and above 3 ng/ml, inhibited the stimulatory effect of PTH (10 nmol/l) on 45Ca release from prelabelled calvarial bones. The inhibitory effect of cholera toxin (0.1 microgram/ml) on 45Ca release was significant after 6 h and the calculated IC50 value at 24 h was 11.2 ng/ml. Cholera toxin (0.1 microgram/ml) also inhibited PTH-stimulated (10 nmol/l) release of Ca2+, inorganic phosphate (Pi), beta-glucuronidase, beta-N-acetylglucosaminidase and degradation of organic matrix (release of 3H from [3H]proline-labelled bones) in 24 h cultures. 45Ca release from bones stimulated by prostaglandin E2 (1 mumol/l) and 1 alpha-hydroxyvitamin D3 (0.1 mumol/l) was also inhibited by cholera toxin (0.3 microgram/ml) in 24-h cultures. The inhibitory effect of cholera toxin on bone resorption was transient, and in long-term cultures (120 h) cholera toxin caused a dose-dependent, delayed stimulation of mineral mobilization (Ca2+, 45Ca, Pi), degradation of matrix and release of the lysosomal enzymes beta-glucuronidase and beta-N-acetylglucosaminidase.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
[The treatment of osteoporosis and bone resorption of alveoli with alendronate in rat model].
OBJECTIVE: To evaluate the anti-osteoporosis effect of alendronate on bone in rat model. METHODS: The osteoporosis and alveolar bone resorption animal model were established in rats. The experimental groups were given alendronate in 5 mg/kg BW by subcutaneous injection after first day of ovariectomy and dental ligature, three times a week for 6 weeks. All the animals were sacrifised 12 weeks after the operation. The blood samples were collected for determination of biochemical indices. The left femora and jaw bones were processed for histomorphometry. The right femora and mendibles were prepared for determination of bone density and bone biodynamics. RESULTS: As compared with the control groups(without alendronate), the values of experimental groups (with alendronate) were all significantly improved on bone density, bone anti-flexure ability and body weight. The alkaline phosphatase, calcium in serum of ovariectomy groups(without alendronate) were obviously increased. In the experimental group, however, these indices were close to normal levels. In histomorphometry, there were little inflammation in gingiva and no obvious bone resorption in the alveolar crests of the experimental groups; but there were obvious gingivitis and alveolar crests resorption of the control groups. CONCLUSIONS: Alendronate can effectively prevent bone loss to reduce osteoporosis in ovariectomized rats and prohibit pathological alveolar bone resorption.
Alendronate↗