Cancer Treatment Dosing Regimens of Zoledronic Acid Result in Near-Complete Suppression of Mandible Intracortical Bone Remodeling in Beagle Dogs

被引:59
作者
Allen, Matthew R. [1 ]
Kubek, Daniel I. [1 ]
Burr, David B. [1 ,2 ,3 ]
机构
[1] Dept Anat & Cell Biol, Indianapolis, IN 46202 USA
[2] Indiana Univ, Sch Med, Dept Orthopaed Surg, Indianapolis, IN USA
[3] Indiana Univ Purdue Univ, Dept Biomed Engn Program, Indianapolis, IN 46202 USA
关键词
BISPHOSPHONATES; CANCER TREATMENT; JAW; REMODELING SUPPRESSION; OSTEONECROSIS; BISPHOSPHONATE-ASSOCIATED OSTEONECROSIS; DOSE-RANGING TRIAL; MICRODAMAGE ACCUMULATION; BIOMECHANICAL PROPERTIES; PROSTATE-CANCER; CORTICAL BONE; PHASE-I; ALENDRONATE; TURNOVER; STRENGTH;
D O I
10.1359/jbmr.090713
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
Bisphosphonate doses used in cancer treatment are substantially higher than those used for osteoporosis. Little is known about the effects of these high doses on tissue-level remodeling suppression. The aim of this study was to assess the effects of cancer dosing regimens of zoledronic acid on tissue-level bone remodeling at different skeletal sites. Skeletally mature female beagle dogs were treated with monthly intravenous infusions of vehicle (VEH, saline) or zoledronic acid (ZOL, 0.067 mg/kg); an additional group of animals was treated daily with oral alendronate (ALN, 0.2 mg/kg/day). Doses of ZOL and ALN were, on a milligram per kilogram basis, consistent with those used for cancer and osteoporosis, respectively. Following either 3 or 6 months of treatment, animals were euthanized, and mandible, rib, and tibia were processed for dynamic bone histology. There was no evidence of oral lesions or bone matrix necrosis in the mandibles of any animals. After 3 months, the rate of intracortical bone remodeling in the mandible was significantly suppressed with ZOL (-95%) compared with VEH; by 6 months, ZOL had produced nearly complete suppression (-99%) compared with VEH. ZOL also significantly suppressed remodeling in the rib cortex at both 3 (-83%) and 6 (-85%) months compared with VEH; tibia cortex bone formation rate was nonsignificantly lower with ZOL treatment (-68% to -75%). Remodeling suppression in ZOL-treated animals was significantly greater than in ALN-treated animals at both the mandible and the rib; ALN and VEH were not different for any of the assessed parameters at any of the sites. Compared across skeletal sites, the absolute level of remodeling suppression with ZOL treatment was significantly greater at sites with higher remodeling, whereas the percent reduction was similar among the sites. These results document nearly complete intracortical remodeling suppression resulting from monthly intravenous zoledronic acid dosing, with changes being most dramatic at the mandible. (C) 2010 American Society for Bone and Mineral Research.
引用
收藏
页码:98 / 105
页数:8
相关论文
共 54 条
[1]
Alendronate reduces bone toughness of ribs without significantly increasing microdamage accumulation in dogs following 3 years of daily treatment [J].
Allen, Matthew R. ;
Reinwald, Susan ;
Burr, David B. .
CALCIFIED TISSUE INTERNATIONAL, 2008, 82 (05) :354-360
[2]
Mandible matrix necrosis in beagle dogs after 3 years of daily oral bisphosphonate treatment [J].
Allen, Matthew R. ;
Burr, David B. .
JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY, 2008, 66 (05) :987-994
[3]
Alterations in canine vertebral bone turnover, microdamage accumulation, and biomechanical properties following 1-year treatment with clinical treatment doses of risedronate or alendronate [J].
Allen, Matthew R. ;
Iwata, Ken ;
Phipps, Roger ;
Burr, David B. .
BONE, 2006, 39 (04) :872-879
[4]
Bisphosphonates and Osteonecrosis of the Jaw: Moving from the Bedside to the Bench [J].
Allen, Matthew R. .
CELLS TISSUES ORGANS, 2009, 189 (1-4) :289-294
[5]
*AM DENT ASS COUNC, 2006, J AM DENT ASSOC, V137, P1144
[6]
Berenson JR, 2001, CANCER, V91, P144, DOI 10.1002/1097-0142(20010101)91:1<144::AID-CNCR19>3.0.CO
[7]
2-Q
[8]
Berenson JR, 2001, CLIN CANCER RES, V7, P478
[9]
Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis [J].
Black, Dennis M. ;
Delmas, Pierre D. ;
Eastell, Richard ;
Reid, Ian R. ;
Boonen, Steven ;
Cauley, Jane A. ;
Cosman, Felicia ;
Lakatos, Peter ;
Leung, Ping Chung ;
Man, Zulema ;
Mautalen, Carlos ;
Mesenbrink, Peter ;
Hu, Huilin ;
Caminis, John ;
Tong, Karen ;
Rosario-Jansen, Theresa ;
Krasnow, Joel ;
Hue, Trisha F. ;
Sellmeyer, Deborah ;
Eriksen, Erik Fink ;
Cummings, Steven R. .
NEW ENGLAND JOURNAL OF MEDICINE, 2007, 356 (18) :1809-1822
[10]
Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures [J].
Black, DM ;
Cummings, SR ;
Karpf, DB ;
Cauley, JA ;
Thompson, DE ;
Nevitt, MC ;
Bauer, DC ;
Genant, HK ;
Haskell, WL ;
Marcus, R ;
Ott, SM ;
Torner, JC ;
Quandt, SA ;
Reiss, TF ;
Ensrud, KE .
LANCET, 1996, 348 (9041) :1535-1541