Inhibition of bone matrix apposition by (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (AHPrBP) in the mouse

Marie, Pierre J.; Hott, M.; Garba, Marie-Thérèse

doi:10.1016/8756-3282(85)90053-5

Cited by 21 publications

(7 citation statements)

References 19 publications

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“…We studied, however, the distribution of the compounds after a single dose and, in addition, the largest doses used in animal experiments have been about equal to those used in the present study (Reitsma 1982;Jung el al. 1984;Marie et al 1985). The present results agree well with the previous findings, that bisphosphonates disappear rapidly from plasma, and that osseous tissue is the main target for the accumulation of the compounds (Bisaz et al 1978;Fleisch 1983, Monkkonen et al 1987).…”

Section: Discussionsupporting

confidence: 93%

Comparison of the Distribution of Three Bisphosphonates in Mice

Mönkkönen

Koponen

Ylitalo

1990

Pharmacology & Toxicology

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The distribution of approximately equipotent doses of 14C-labelled clodronate (0.1 mmol/kg), etidronate (0.1 mmol/kg), and amidronate (0.015 mmol/kg), and also an equimolar dose of amidronate (0.1 mmol/kg), was studied in mice by measuring the 14C-activities in various tissues up to 360 days after a single intravenous injection. With the higher dose of amidronate the distribution could be, however, monitored only for 7 days because of the toxicity of the drug. The results indicate that there are major differences in the deposition of the bisphosphonates into soft tissues, while the disappearance from plasma and incorporation into bone are quite similar in terms of percentage of dose per g of tissue. However, the binding capacity of bone for clodronate and etidronate is many times greater than that for amidronate expressed as nmol of the drug per g of tissue. Amidronate deposits in the spleen and liver of mice, when injected in saline, whereas clodronate and etidronate do not. This agrees with the suggestion that amidronate, but not the other two, can interfere with the mononuclear phagocyte system of spleen and liver.

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Section: Discussionsupporting

confidence: 93%

Comparison of the Distribution of Three Bisphosphonates in Mice

Mönkkönen

Koponen

Ylitalo

1990

Pharmacology & Toxicology

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“…Bone formation activity as measured by the osteoid parameters and MAR was severely depressed by APD. Similar findings have been reported [20]. This shows that APD not only inhibits bone resorption, but depresses also bone formation.…”

Section: Discussionsupporting

confidence: 88%

Sequential treatment of osteopenic ovariectomized rats with parathyroid hormone (1-34) fragment and pamidronate

1994

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Abstract:Low doses of PTH(1-34) stimulate bone formation in rats but the effect is reversed after PTH withdrawal. This study shows that this reversal is prevented when sequential PTH-APD treatment is employed. Seventy 3-month-old female wistar rats were ovariectomized, and fed with regular rodent chow and water ad libitum. Twelve weeks later they were divided into seven groups and treated as follows: GI: 3w PTH (5d/w, 20ttg/kg/d sc). G2: 3w saline (5d/w, sc). G3: lw ADP (5d/w, 250 #g/kg/d sc) -~ 3w PTH. G4: lw APD -> 3w saline. G5: 3w PTH --> 5d APD -~ 3w untreated. G6: 3w PTH -~ 5d saline --> 3w untreated. G7: 3w saline --> 5d saline -~ 3w untreated. Two tetracycline labels (2 weeks apart) were administered to each rat before killing. Static and dynamic bone histomorphometries were performed on trichrome stained and unstained sections of distal femoral metaphysis. Cancellous bone volume (Cn.BV/TV) results showed that, when compared with the osteopenie controls (G2, G7), PTH stimulated bone formation (G1) but the effect was reversed after drug withdrawal (G6) and that APD post-treatment prevented this reversal (G5). The results also showed that APD pre-treatment (G3) was as effective as APD post-treatment (GS) in building up cancellous bone, but APD alone (G4) was significantly less effective. Mineral apposition rates (MAR) showed that while APD suppressed bone formation (G4, G5), PTH was able to stimulate bone formation even after APD treatment (G3).

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“…Another characteristic was an increased number of TRAP + multinucleated cells within the marrow spaces. Marie et al reported such accumulation of TRAP + multinucleated cells, not in contact with the bone surface, in mice treated with NBPs [25]. TRAP expression is not specific to the osteoclast phenotype, as other monocyte-derived cells, such as activated and inflammatory macrophages, also express TRAP in bone marrow [26].…”

Section: Discussionmentioning

confidence: 99%

Bisphosphonate-associated osteonecrosis of the jaw: A key role of inflammation?

Lesclous

Najm

Carrel

et al. 2009

Bone

194

140

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Osteonecrosis of the jaw (ONJ) can be associated with nitrogen-containing bisphosphonates (NBPs) therapy. Various mechanisms of NBP-associated ONJ have been proposed and there is currently no consensus of the underlying pathogenesis. The detailed medical and dental histories of 30 ONJ patients treated with NBPs for malignant diseases (24) or osteoporosis (6) were analyzed. The necrotic bone was resected and analyzed histologically after demineralization. In 10 patients the perinecrotic bone was also resected and processed without demineralization. Alveolar bone samples from 5 healthy patients were used as controls. In 14 ONJ patients, serial technetium-99m-methylene diphosphonate scintigraphic scans were also available and confronted to the other data. Strong radionuclide uptake was detected in some patients several months before clinical diagnosis of ONJ. The medullary spaces of the necrotic bone were filled with bacterial aggregates. In the perinecrotic bone, the bacteria-free bone marrow characteristically showed an inflammatory reaction. The number of medullary inflammatory cells taken as an index of inflammation allowed us to discriminate two inflammation grades in the ONJ samples. Low-grade inflammation, characterized by marrow fibrosis and low inflammatory cells infiltration, increased numbers of TRAP + monoand multineacleated cells was seen in patients with bone exposure b 2 cm 2 . High-grade inflammation, associated with larger lesions, showed amounts of tartrate-resistant acid phosphatase + /calcitonin receptor − mono-and multinucleated cells, osteocyte apoptosis, hypervascularization and high inflammatory cell infiltration. The clinical extent of ONJ was statistically linked to the numbers of inflammatory cell. Taken together these data suggest that bone necrosis precedes clinical onset and is an inflammation-associated process. We hypothesize that from an initial focus, bone damage spreads centrifugally, both deeper into the jaw and towards the mucosa before the oral bone exposure and the clinical diagnosis of ONJ.

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Inhibition of bone matrix apposition by (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (AHPrBP) in the mouse

Cited by 21 publications

References 19 publications

Comparison of the Distribution of Three Bisphosphonates in Mice

Comparison of the Distribution of Three Bisphosphonates in Mice

Sequential treatment of osteopenic ovariectomized rats with parathyroid hormone (1-34) fragment and pamidronate

Bisphosphonate-associated osteonecrosis of the jaw: A key role of inflammation?

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