骨硬化(OPT)表示破骨细胞在整个生长过程中无法吸收骨和软骨细胞以去除钙化的骨软骨的后果。导致骨骼建模受损,重塑,增长损害了延髓空间的扩大,头骨的形成,和颅孔扩张。因此,脊髓性贫血,颅内压升高,严重时,颅神经麻痹会使OPT复杂化。由于畸形导致的骨质骨折,重塑无法编织皮质骨和小梁的胶原基质,矿化生长板软骨的持久性,羟基磷灰石晶体的“硬化”,和骨骼微裂纹延迟愈合。牙齿可能无法爆发。现在人们普遍认识到,OPT是由通常涉及破骨细胞功能的基因的种系功能丧失突变引起的,尤其是破骨细胞形成所必需的基因。此外,然而,2003年,我们发表了一个病例报告,证明儿童期长期过量服用抗吸收性氨基二膦酸盐帕米膦酸钠可充分阻断破骨细胞和软骨细胞活性,从而概括OPT的骨骼特征.在这里,我们通过对成骨不全症患儿反复服用高剂量的氨基二膦酸唑来膦酸(唑来膦酸),阐明了药物诱导的OPT骨形成的骨骼变化,进一步纳入了药物诱导的OPT证据.
Osteopetrosis (OPT) denotes the consequences from failure of osteoclasts to resorb bone and chondroclasts to remove calcified physeal cartilage throughout growth. Resulting impairment of skeletal modeling, remodeling, and growth compromises widening of medullary spaces, formation of the skull, and expansion of cranial foramina. Thus, myelophthisic anemia, raised intracranial pressure, and cranial nerve palsies complicate OPT when severe. Osteopetrotic bones fracture due to misshaping, failure of remodeling to weave the collagenous matrix of cortical osteons and trabeculae, persistence of mineralized growth plate cartilage, \"hardening\" of hydroxyapatite crystals, and delayed healing of skeletal microcracks. Teeth may fail to erupt. Now it is widely appreciated that OPT is caused by germline loss-of-function mutation(s) usually of genes involved in osteoclast function, but especially rarely of genes necessary for osteoclast formation. Additionally, however, in 2003 we published a case report demonstrating that prolonged excessive dosing during childhood of the antiresorptive aminobisphosphonate pamidronate can sufficiently block osteoclast and chondroclast activity to recapitulate the skeletal features of OPT. Herein, we include further evidence of drug-induced OPT by illustrating osteopetrotic skeletal changes from repeated administration of high doses of the aminobisphosphonate zoledronic acid (zoledronate) given to children with osteogenesis imperfecta.