Zoledronate Effects on Systemic and Jaw Osteopenias in Ovariectomized Periostin-Deficient Mice

被引:30
作者
Bonnet, Nicolas [1 ]
Lesclous, Philippe [2 ,3 ]
Saffar, Jean Louis [2 ]
Ferrari, Serge [1 ]
机构
[1] Univ Hosp Geneva, Dept Internal Med Specialties, Div Bone Dis, Geneva, Switzerland
[2] Univ Paris 05, Fac Chirurg Dent, Lab Pathol Imagerie & Biotherapie Organe Dent EA, Paris, France
[3] LUNAM Univ, STEP Skeletal Tissue Engn & Physiopathol Grp, Hotel Dieu Hosp,Univ Nantes,Sch Dent, INSERM UMRS 791,LIOAD Lab Ingn Osteoarticulaire &, Nantes, France
基金
瑞士国家科学基金会;
关键词
BISPHOSPHONATE-ASSOCIATED OSTEONECROSIS; ALVEOLAR BONE-RESORPTION; PLACEBO-CONTROLLED TRIAL; EXPERIMENTAL PERIODONTITIS; POSTMENOPAUSAL WOMEN; PREVENTIVE MEASURES; CANCER-PATIENTS; IN-VIVO; DISEASE; RATS;
D O I
10.1371/journal.pone.0058726
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
Osteoporosis and periodontal disease (PD) are frequently associated in the elderly, both concurring to the loss of jaw alveolar bone and finally of teeth. Bisphosphonates improve alveolar bone loss but have also been associated with osteonecrosis of the jaw (ONJ), particularly using oncological doses of zoledronate. The effects and therapeutic margin of zoledronate on jaw bone therefore remain uncertain. We reappraised the efficacy and safety of Zoledronate (Zol) in ovariectomized (OVX) periostin (Postn)-deficient mice, a unique genetic model of systemic and jaw osteopenia. Compared to vehicle, Zol 1M (100 mu g/kg/month) and Zol 1W (100 mu g/kg/week) for 3 months both significantly improved femur BMD, trabecular bone volume on tissue volume (BV/TV) and cortical bone volume in both OVX Postn(+/+) and Postn(-/-) (all p<0.01). Zol 1M and Zol 1W also improved jaw alveolar and basal BV/TV, although the highest dose (Zol 1W) was less efficient, particularly in Postn(-/-). Zol decreased osteoclast number and bone formation indices, i.e. MAR, MPm/BPm and BFR, independently in Postn(-/-) and Postn(+/+), both in the long bones and in deep jaw alveolar bone, without differences between Zol doses. Zol 1M and Zol 1W did not reactivate inflammation nor increase fibrous tissue in the bone marrow of the jaw, whereas the distance between the root and the enamel of the incisor (DRI) remained high in Postn(-/-) vs Postn(+/+) confirming latent inflammation and lack of crestal alveolar bone. Zol 1W and Zol 1M decreased osteocyte numbers in Postn(-/-) and Postn(+/+) mandible, and Zol 1W increased the number of empty lacunae in Postn(-/-), however no areas of necrotic bone were observed. These results demonstrate that zoledronate improves jaw osteopenia and suggest that in Postn(-/-) mice, zoledronate is not sufficient to induce bone necrosis.
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页数:10
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