Serum Markers of Bone Turnover and Angiogenesis in Patients With Bisphosphonate-Related Osteonecrosis of the Jaw After Discontinuation of Long-Term Intravenous Bisphosphonate Therapy.
Serum Markers of Bone Turnover and Angiogenesis in Patients With Bisphosphonate-Related Osteonecrosis of the Jaw After Discontinuation of Long-Term Intravenous Bisphosphonate Therapy.
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DOI：
10.1016/j.joms.2015.09.028
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发表时间：
2016-04
期刊：
影响因子：
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通讯作者：
Gopalakrishnan R
中科院分区：
文献类型：
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作者：
Thumbigere-Math V;Michalowicz BS;Hughes PJ;Basi DL;Tsai ML;Swenson KK;Rockwell L;Gopalakrishnan R
分析停止长期静脉双磷酸盐（BP）治疗的双磷酸盐相关性颌骨骨坏死（BRONJ）患者的骨转换、血管生成、内分泌功能和炎症的血清标志物。血清样本来自25名停止长期静脉BP治疗平均11.4±8.7个月的BRONJ患者和48名继续接受静脉BP治疗的非BRONJ对照。分析样本的总碱性磷酸酶（ALP）、骨特异性碱性磷酸酶（BALP）、骨钙素（OCN）、C端肽（CTX）、血管内皮生长因子（VEGF）、三碘甲状腺原氨酸（T3）、甲状腺素（T4）、促甲状腺激素（TSH）、25-羟基维生素D和C反应蛋白（CRP）。BRONJ受试者的BP输注平均次数显著高于对照组（38.4±26.3次输注vs 18.8±7.2次，p<0.0001）;然而，两组之间的BP治疗持续时间无显著差异（p=0.23）。总体而言，BRONJ受试者和对照组之间的任何标志物均无显著差异（所有p值≥ 0.16）。根据平均年龄和血压输注量匹配BRONJ受试者和对照组（BRONJ，n=10，对照组，n=48）的亚组分析中，BRONJ受试者的log 10 VEGF（2.9±0.4 vs 2.4±0.4，p=<0.001）和CRP（34±26 vs 13±8，p=<0.01）水平显著高于对照组。在BRONJ受试者中，没有血清标志物与BP停药的持续时间相关。停止长期静脉BP治疗的BRONJ受试者的骨转换和内分泌标志物与接受静脉BP治疗的非BRONJ对照相似。然而，血管生成和炎症标志物在停止长期静脉BP治疗的BRONJ受试者中较高。在BRONJ受试者中，BP延长的骨骼半衰期可能会在静脉内BP治疗停止后数年内抑制骨转换标志物，这表明对骨稳态的影响延长。
To analyze serum markers of bone turnover, angiogenesis, endocrine function, and inflammation in bisphosphonate-related osteonecrosis of the jaw (BRONJ) patients who discontinued long-term intravenous bisphosphonate (BP) therapy. Serum samples were obtained from 25 BRONJ patients who had discontinued long-term intravenous BP therapy for an average of 11.4±8.7 months and 48 non-BRONJ controls who continued receiving intravenous BP therapy. Samples were analyzed for total alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP), osteocalcin (OCN), C-telopeptide (CTX), vascular-endothelial growth factor (VEGF), triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), 25-hydroxyvitamin D, and C-reactive protein (CRP). The mean number of BP infusions was significantly higher in BRONJ subjects compared with controls (38.4±26.3 infusions vs 18.8±7.2, p<0.0001); however, the duration of BP therapy was not significantly different between the groups (p=0.23). Overall, there were no significant differences in any of the markers between BRONJ subjects and controls (all p values ≥ 0.16). In a subgroup analysis that matched BRONJ subjects and controls according to mean age and BP infusions (BRONJ, n=10 and controls, n=48), log10VEGF (2.9±0.4 vs 2.4±0.4, p=<0.001) and CRP (34±26 vs 13±8, p=<0.01) levels were significantly higher in BRONJ subjects compared with controls. Within BRONJ subjects, none of the serum markers were correlated with duration of BP discontinuation. Bone turnover and endocrine markers in BRONJ subjects who discontinue long-term intravenous BP therapy are similar to non-BRONJ controls receiving intravenous BP therapy. However, angiogenesis and inflammation markers are higher in BRONJ subjects who discontinue long-term intravenous BP therapy. The prolonged skeletal half-life of BPs may suppress bone turnover markers in BRONJ subjects for several years following discontinuation of intravenous BP therapy, suggesting an extended effect on bone homeostasis.