AbstractNitrogen‐containing bisphosphonates (N‐BPs) inhibit bone resorption by preventing osteoclast activity. Most clinically used BPs are hydroxybisphosphonates with the exception of incadronate, which belongs to the class of aminomethylidenebisphosphonic acids. The aim of this study was to evaluate the antiproliferative activity of two previously reported aminobisphosphonates (WG8185B2 and WG9001B) in combination with doxorubicin and cisplatin toward J774E cells (a model of osteoclast precursors in vitro). WG8185B2 and WG9001B BPs enhanced the cytotoxic activity of doxorubicin and cisplatin, especially when applied 24 hr prior to cytostatics. The antiproliferative effect of studied BPs was related to the changes in cell cycle progression. WG8185B2 leads to significant accumulation of J774E cells in S phase, whereas WG9001B causes transient arrest in G2/M phase, followed by an increase in the percentage of cells in S phase. Moreover, WG8185B2 and WG9001B BPs showed enhanced proapoptotic activity in osteoclast precursors, which was manifested by an increase in caspase‐3 activity and percentage of apoptotic cells. In addition, both compounds influenced the motility of J774E cells. The exact molecular mechanism of action of examined BPs remains to be determined; however, results show an interesting biological activity of these compounds, which may be of interest in the context of antiresorptive therapy.

17 Nov 2009·Zhonghua yi xue za zhi

[Long-term and high-dose bisphosphonate administration causes no bone over-mineralization].

Article

Author: Tasuku Mashiba ; Satoshi Mori ; Chao Liu ; Xin Yang ; Yong-ping Cao

OBJECTIVETo evaluate the effects of long-term bisphosphonate administration (incadronate) upon the mean degree of secondary bone mineralization.METHODSThirty adult beagles were divided randomly into three groups of CNT, YML and YMH based upon their body weights (5 males and 5 females in each group). Animals in CNT were orally given lactose 12 mg x kg(-1) x d(-1) while those in YML and YMH were orally given incadronate disodium at doses of 0.3 mg x kg(-1) x d(-1) and 0.6 mg x kg(-1) x d(-1) respectively. The dosing procedure lasted for three years. Prior to sacrifices, all animals were double-labeled intravenously with oxytetracycline hydrochloride (20 mg x kg(-1)). After necropsy, the left 9th ribs were excised for evaluation.RESULTSHistomorphometry showed that activation frequency in YML and YMH [(4.93 +/- 0.92)/mm(2) and (2.50 +/- 0.78)/mm(2)] were significantly lower than that in CNT (7.83 +/- 0.96)/mm(2) per year. The mean degree of mineralization in bone in YML and YMH (1.40 +/- 0.12, 1.48 +/- 0.09) were significantly higher than CNT (1.07 +/- 0.06). The increments were 31% and 38% respectively.CONCLUSIONLong-term and high-dose bisphosphonate administration significantly suppresses bone turnover so as to increase the degree of bone mineralization. But there is no resulting bone over-mineralization. (incadronate) administration on the mean degree of secondary mineralization in bone.

01 Sep 2008·Osteoporosis InternationalQ2 · MEDICINE

Collagen maturity, glycation induced-pentosidine, and mineralization are increased following 3-year treatment with incadronate in dogs

Q2 · MEDICINE

Article

Author: M. Saito ; T. Mashiba ; K. Marumo ; S. Komatsubara ; S. Mori

Collagen cross-linking is a determinant of bone quality. A three-year treatment of bisphosphonate-incadronate disodium-in beagles increased degree of mineralization, collagen maturity, and pentosidine, a compound with advanced glycation end products. The treatment had no effect on the total amount of enzymatic cross-link formation.INTRODUCTIONCollagen cross-linking is a determinant of bone quality. Recently, we reported that long-term treatment with bisphosphonate increased microdamage accumulation. The aim of this study was to clarify the effect of a three-year treatment with bisphosphonate on degree of mineralization and immature and mature enzymatic cross-links and non-enzymatic collagen cross-link, pentosidine, in cortical bone in the same dogs.METHODSTwenty-nine 1-year-old beagles (15 males, 14 females) were divided into three groups that daily were given vehicle or incadronate at doses of 0.3 or 0.6 mg/kg/day orally for three years. A cortex of a rib was fractionated into low- and high-density portions. The contents of calcium, phosphorus, enzymatic immature and mature cross-links, and the non-enzymatic glycation product pentosidine were determined in each fraction.RESULTSCalcium, phosphorus, and pentosidine contents and the ratio of mature to immature cross-links increased significantly with incadronate in a dose-dependent manner, but the total amount of enzymatic cross-links was unchanged. The pentosidine content correlated inversely with cortical activation frequency (p < 0.01).CONCLUSIONLong-term suppression of bone remodeling by bisphosphonate increases degree of mineralization, collagen maturity, and non-enzymatic cross-linking.

100 Deals associated with Incadronate Disodium

External Link

KEGG	Wiki	ATC	Drug Bank
D07123	Incadronate Disodium	M05BA	DB06255

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Humoral Hypercalcemia of Malignancy	JP	-	20 Nov 1997
Hypercalcemia	JP	Astellas Pharma, Inc.	01 Jan 1997
Osteoporosis	JP	Astellas Pharma, Inc.	01 Jan 1997
Pain	JP	Astellas Pharma, Inc.	01 Jan 1997
Periodontitis	JP	Astellas Pharma, Inc.	01 Jan 1997

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