Etidronate is a non-nitrogen-containing bisphosphonate. Because it binds with calcium and inhibits crystal formation and dissolution, it was considered by Procter & Gamble as an additive to toothpaste (to prevent build-up of tartar) and detergent (to bind calcium and increase sudsing in "hard" water). The first clinical use (1968) was for fibrodysplasia ossificans progressiva. The first approved clinical use (1977) was for treatment of Paget's disease of bone. Other approved indications are hypercalcemia of malignancy and heterotopic ossification, with a host of off-label uses (including fibrous dysplasia, periodontal disease, multiple myeloma, neuropathic arthropathy, pulmonary microlithiasis, diabetic retinopathy, bone metastases, melorheostosis, urinary stone disease, periodontal disease, etc.). Unique among bisphosphonates, etidronate (oral therapy) results in hyperphosphatemia, increased tubular reabsorption of phosphorus and increased levels of 1,25-dihydroxyvitamin D. The dose that reduces bone resorption is close to the dose that impairs mineralization; prolonged high-dose use can result in osteomalacia and bone fractures. Intermittent cyclic etidronate for osteoporosis resulted in favorable changes in bone density and histomorphometry (no mineralization defect) as well as a decrease in vertebral fracture rates in postmenopausal women with osteoporosis. Later studies showed similar effects in men with osteoporosis and patients with glucocorticoid-induced osteoporosis. Although its use for osteoporosis has given way to newer bisphosphonates and other agents, because of its unique properties, it remains the bisphosphonate of choice for treatment of heterotopic ossification.

中文翻译：

---

依替膦酸盐的历史

依替膦酸盐是一种不含氮的双膦酸盐。因为它与钙结合并抑制晶体形成和溶解，宝洁公司将其视为牙膏的添加剂（防止牙垢积聚）和洗涤剂（结合钙并增加“硬”水中的泡沫）。第一次临床使用（1968 年）是针对进展性骨化纤维发育不良。第一个批准的临床用途（1977 年）是用于治疗佩吉特骨病。其他批准的适应症是恶性肿瘤和异位骨化的高钙血症，具有许多标签外用途（包括纤维发育不良、牙周病、多发性骨髓瘤、神经性关节病、肺微石症、糖尿病视网膜病变、骨转移、melorheostosis、泌尿系结石病、牙周病， 等等。）。在双膦酸盐中独一无二，依替膦酸盐（口服治疗）导致高磷血症，增加肾小管对磷的重吸收和增加 1,25-二羟基维生素 D 的水平。减少骨吸收的剂量接近于损害矿化的剂量；长期高剂量使用可导致骨软化和骨折。用于骨质疏松症的间歇性环依替膦酸盐导致骨密度和组织形态计量学的有利变化（无矿化缺陷）以及患有骨质疏松症的绝经后妇女的椎骨骨折率降低。后来的研究表明，男性骨质疏松症和糖皮质激素诱发的骨质疏松症患者有类似的效果。尽管它用于治疗骨质疏松症已让位于较新的双膦酸盐和其他药物，但由于其独特的性质，