Division of Oral Biology, School of Dentistry, University of São Paulo, Brazil.
Eur J Histochem. 2012 May 25;56(2):e24. doi: 10.4081/ejh.2012.24.
The replacement of the calcified cartilage by bone tissue during the endochondral ossification of the mandibular condyle is dependent of the resorbing activity of osteoclats. After partial resorption, calcified cartilage septa are covered by a primary bone matrix secreted by osteoblasts. Osteoadherin (OSAD) is a small proteoglycan present in bone matrix but absent in cartilage during the endochondral ossification. The aim of this study was to analyze the effect of alendronate, a drug known to inhibit bone resorption by osteoclasts, on the endochondral ossification of the mandibular condyle of young rats, by evaluating the distribution of osteoclasts and the presence of OSAD in the bone matrix deposited. Wistar newborn rats (n=45) received daily injections of alendronate (n=27) or sterile saline solution as control (n=18) from the day of birth until the ages of 4, 14 and 30 days. At the days mentioned, the mandibular condyles were collected and processed for transmission electron microscopy analysis. Specimens were also submitted to tartrate resistant acid phosphatase (TRAP) histochemistry and ultrastructural immunodetection of OSAD. Alendronate treatment did not impede the recruitment and fusion of osteoclasts at the ossification zone during condyle growth, but they presented inactivated phenotype. The trabeculae at the ossification area consisted of cartilage matrix covered by a layer of primary bone matrix that was immunopositive to OSAD at all time points studied. Apparently, alendronate impeded the removal of calcified cartilage and maturation of bone trabeculae in the mandibular ramus, while in controls they occurred normally. These findings highlight for giving attention to the potential side-effects of bisphosphonates administered to young patients once it may represent a risk of disturbing maxillofacial development.
骺软骨的骨化过程中，破骨细胞的吸收活性决定了钙化软骨被骨组织取代的过程。在部分吸收后，钙化软骨隔被成骨细胞分泌的初级骨基质覆盖。骨粘连蛋白（OSAD）是一种小的蛋白聚糖，在骺软骨骨化过程中存在于骨基质中，但不存在于软骨中。本研究旨在分析阿仑膦酸钠（一种已知可抑制破骨细胞吸收的药物）对幼年大鼠下颌骨髁突骺软骨骨化的影响，通过评估破骨细胞的分布和骨基质中 OSAD 的存在来评估。新生 Wistar 大鼠（n=45）从出生后每天接受阿仑膦酸钠（n=27）或无菌生理盐水（n=18）注射，直到 4、14 和 30 天。在这些天，收集下颌骨髁突并进行透射电镜分析。标本还进行了抗酒石酸酸性磷酸酶（TRAP）组织化学和 OSAD 的超微结构免疫检测。阿仑膦酸钠治疗并没有阻止在髁突生长过程中骨化区破骨细胞的募集和融合，但它们表现出失活的表型。在骨化区的小梁由软骨基质组成，其被一层初级骨基质覆盖，在所有研究的时间点都对 OSAD 呈免疫阳性。显然，阿仑膦酸钠阻碍了下颌支钙化软骨的去除和骨小梁的成熟，而在对照组中，这些过程正常发生。这些发现强调了在给年轻患者使用双膦酸盐时要注意其潜在的副作用，因为这可能会干扰颌面部的发育。
