Apd in paget's disease of bone role of the mononuclear phagocyte system?

Bijvoet, O. L. M.; Frijlink, W. B.; Jie, Kon‐Siong G.; Linden, H. Der Van; Meijer, C. J. L. M.; Mulder, H.; Paassen, H. C. Van; Reitsma, Pieter H.; Velde, J. te; Vries, E. de; Wey, J. P. Der Van

doi:10.1002/art.1780231018

Cited by 125 publications

(34 citation statements)

References 35 publications

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“…These compounds have been shown to decrease inflammatory activity and joint destruction in animal models of arthritis (31,32), whereas small open as well as controlled studies in RA patients have suggested that they decrease clinical signs of arthritis activity (16,(33)(34)(35). In the present study, an effect of pamidronate on disease activity or the progression of radiologic signs of joint destruction could not be substantiated.…”

Section: Discussioncontrasting

confidence: 60%

Increased bone mass with pamidronate treatment in rheumatoid arthritis. Results of a three‐year randomized, double‐blind trial

Eggelmeijer

Papapoulos

Paassen

et al. 1996

Arthritis & Rheumatism

119

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Objective. Osteoporosis is a frequent complication of rheumatoid arthritis (RA). We therefore investigated the effect of oral pamidronate therapy as a specific bone‐sparing agent in RA. Methods. The study design was a 3‐year randomized, double‐blind trial of 300 mg oral pamidronate/day compared with placebo in 105 RA patients. Bone mineral density (BMD) measured at 12‐month intervals was the primary efficacy parameter. Results. In 3 years, lumbar spine and forearm BMD increased significantly in the pamidronate‐treated group (by 8.4 ± 6.9% [mean ± SEM] [P < 0.0001] and 5.2 ± 6.5% [P < 0.005], respectively), compared with nonsignificant changes in the placebo‐treated patients (increase of 0.6 ± 5.2% and decrease of 1.2 ± 5.8%, respectively). Femoral neck BMD increased in the pamidronate‐treated group (by 2.6 ± 8.6%) and decreased significantly in the placebo‐treated group (by 4.0 ± 1.3% [P < 0.005]). The changes in BMD with time at all 3 measurement sites were significantly different between the treatment groups (P < 0.0001). Changes in radiographic signs of joint damage and in disease activity were similar in the 2 groups. Conclusion. The present study provides the first evidence that long‐term treatment with an orally administered bisphosphonate overcomes bone loss and increases bone mass when compared with placebo. This finding may have significance with regard to the treatment of patients with RA.

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Section: Discussioncontrasting

confidence: 60%

Increased bone mass with pamidronate treatment in rheumatoid arthritis. Results of a three‐year randomized, double‐blind trial

Eggelmeijer

Papapoulos

Paassen

et al. 1996

Arthritis & Rheumatism

119

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“…APD and C12MDP do not behave identically in vivo (9) and other differences in the mechanisms of action of these compounds are evident in the present in vitro study. C12MDP appears to work as a cytotoxin in the presence of bone, and this seems adequate to account for the diminution in macrophage-mediated resorption reported above and, perhaps, in animals treated with this P-C-P. APD, on the other hand, suppresses resorption without killing the resorbing cells and without the intervention by bone.…”

Section: Resultscontrasting

confidence: 51%

“…Interestingly, APD effectively decreases bone resorption in vivo at much lower doses than does C12MDP. There is no clear explanation for this difference in potency, but it may relate to the observed effects of APD on the mononuclear phagocyte system (9). Cells of the mononuclear phagocyte system (MPS) have the potential to regulate osteoclast activity (e.g., by producing prostaglandin E2) and APD might alter this aspect of MPS function.…”

Section: Introductionmentioning

confidence: 99%

Differential Action of the Bisphosphonates (3-Amino-1-Hydroxypropylidene)-1,1-Bisphosphonate (APD) and Disodium Dichloromethylidene Bisphosphonate (Cl2MDP) on Rat Macrophage-mediated Bone Resorption In Vitro

Teitelbaum²,

et al. 1982

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A B S T R A C T The bisphosphonates (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) and disodium dichloromethylidene bisphosphonate (Cl2MDP) effectively inhibit the accelerated bone resorption associated with some skeletal disorders, e.g., Paget's disease. However, it has not been established whether these compounds exert their inhibitory effect by rendering the bone mineral more resistant to degradation, by diminishing the activity of resorbing cells, or through some combination of both activities. In this study, we have tested these possibilities using an in vitro resorption assay system consisting of elicited rat peritoneal macrophages co-cultured with particles of 45Ca-labeled, devitalized rat bone. This assay system permits the quantitative assessment of the action of APD and Cl2MDP on the two major phases of bone resorption (cell-substrate attachment and osteolysis) under circumstances where the drugs are present continuously or, most importantly for the issues in question, after the separate pretreatment of the particles or the resorbing cells.Our data indicate that (a) Both APD and C12MDP at concentrations 25 X 106 M diminish macrophagemediated 45Ca release (i.e., bone resorption) in a log Received for publication 22 dose-dependent fashion. (b) A 10-min pretreatment of bone particles with either bisphosphonate (P-C-P) similarly inhibits resorptive activity, but is most pronounced with Cl2MDP. However, only APD is effective in reducing resorption when cells are preincubated (for 24 h) with P-C-P. (c) In cultures containing both labeled and unlabeled bone, significant inhibition occurs only when the labeled particles are coated with P-C-P (indicating that the action of P-C-P-treated bone is highly localized). (d) P-C-P does not diminish cell-bone particle attachment, an essential step in the resorptive process. On the other hand, delaying the addition of P-C-P until after cell-bone attachment is completed significantly reduces the resorption-inhibiting effect of these compounds. (e) C12MDP reduces culture DNA content in proportion to its inhibitory effect on resorption, and both the inhibitory and cytotoxic actions of this P-C-P are dependent upon the presence of bone. On the other hand, APD is cytotoxic only at very high concentrations (10-4 M), acts independently of the presence of bone, and inhibits resorption without killing cells.We conclude that the mechanisms of action of APD and C12MDP are markedly different. C12MDP is a potent cytotoxin in the presence of bone and apparently exerts its inhibitory effect in this manner. APD is noncytotoxic at levels adequate to suppress resorption and, therefore, must inhibit macrophage activity by some other mechanism. Neither P-C-P appears to limit resorption by decreasing the solubility of mineralized bone matrix.J. Clin. Invest.

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“…It was originally thought that PCPs might inhibit bone resorption through physicochemical effects on hydroxyapatite dissolution (1 1). More recently it has become clear that PCPs have a wide variety of effects on cells thought to be involved in bone turnover, such as osteoblasts (12,13) and cells belonging to the mononuclear phagocyte system (14)(15)(16). However, the relative potencies with which different PCPs inhibit crystal dissolution or cause most of their cellular effects in vitro differ from the relative potencies of these compounds in experimental animals or as therapeutic agents in man.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of osteoclast-like cell formation by bisphosphonates in long-term cultures of human bone marrow.

Hughes¹,

MacDonald²,

Russell³

et al. 1989

J. Clin. Invest.

328

154

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Bisphosphonates inhibit bone resorption in vivo and in vitro by unknown mechanisms. The effect of bisphosphonates on the formation of osteoclasts from their mononuclear hematopoietic precursors was investigated using human long-term marrow cultures in which multinucleated cells form that express most of the known features of the osteoclast phenotype (e.g., bone resorption, tartrate-resistant acid phosphatase, calcitonin responsiveness, and reactivity with specific MAbs). The five bisphosphonates that were tested strongly inhibited 1,25-dihydroxyvitamin D3-stimulated formation of these cells with the same relative pqtencies as they inhibit ione resorption in vivo. Two representative compounds (3-amino-1-hydroxypropylidene-1,1-bisphosphonate and dichloromethylene bisphosphonate) failed to inhibit the proliferation of precursors of the osteoclast-like cells. However, these compounds decreased the proportion of mononuclear and multinucleated cells expressing an osteoclast antigen, thus suggesting a degree of specificity for cells of the osteoclast lineage. We conclude that bisphosphonates are potent inhibitors of osteoclast-like cell formation in long-term human mprrow cultures, #nd that this may be related to their ability to inhibit bone resorption in vivo.

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Apd in paget's disease of bone role of the mononuclear phagocyte system?

Cited by 125 publications

References 35 publications

Increased bone mass with pamidronate treatment in rheumatoid arthritis. Results of a three‐year randomized, double‐blind trial

Increased bone mass with pamidronate treatment in rheumatoid arthritis. Results of a three‐year randomized, double‐blind trial

Differential Action of the Bisphosphonates (3-Amino-1-Hydroxypropylidene)-1,1-Bisphosphonate (APD) and Disodium Dichloromethylidene Bisphosphonate (Cl2MDP) on Rat Macrophage-mediated Bone Resorption In Vitro

Inhibition of osteoclast-like cell formation by bisphosphonates in long-term cultures of human bone marrow.

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