Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA.
Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA.
Bone. 2021 Jan;142:115711. doi: 10.1016/j.bone.2020.115711. Epub 2020 Oct 24.
Bisphosphonates (BPs) are characterized by their ability to bind strongly to bone mineral and inhibit bone resorption. However, BPs exert a wide range of pharmacological activities beyond the inhibition of bone resorption, including the inhibition of cancer cell metastases and angiogenesis and the inhibition of proliferation and apoptosis in vitro. Additionally, the inhibition of matrix metalloproteinase activity, altered cytokine and growth factor expression, as well as reductions in parameters of pain have also been reported. In humans, clinical BP use has transformed the treatment of post-menopausal osteoporosis, rare bone diseases such as osteogenesis imperfecta, as well as multiple myeloma and metastatic breast and prostate cancer, albeit not without infrequent but significant adverse events. Despite the well-characterized health benefits of BP use in humans, the evidence-base for the therapeutic efficacy of BPs in veterinary medicine is, by comparison, limited. Notwithstanding, BPs are used widely in small animal veterinary practice for the medical management of hyperparathyroidism, idiopathic hypercalcemia in cats, as well as for the palliative care of bone tumors which are common in dogs, and in particular, primary bone tumors such as osteosarcoma. Palliative BP treatment has also recently increased in veterinary oncology to alleviate tumor-associated bone pain. In equine veterinary practice, non-nitrogen-containing BPs are FDA-approved to control clinical signs associated with navicular syndrome in adult horses. However, there are growing concerns regarding the off-label use of BPs in juvenile horses. Here we discuss the current understanding of the strengths, weaknesses and current controversies surrounding BP use in veterinary medicine to highlight the future utility of these potentially beneficial drugs.
双膦酸盐(BPs)的特点是能够与骨矿物质紧密结合并抑制骨吸收。然而,BPs 具有广泛的药理活性,不仅限于抑制骨吸收,还包括抑制癌细胞转移和血管生成,以及抑制体外细胞增殖和凋亡。此外,还报道了抑制基质金属蛋白酶活性、改变细胞因子和生长因子表达以及减少疼痛参数等作用。在人类中,临床 BP 的使用改变了绝经后骨质疏松症、成骨不全等罕见骨骼疾病以及多发性骨髓瘤和转移性乳腺癌和前列腺癌的治疗方法,尽管并非没有罕见但严重的不良事件。尽管 BP 在人类中的使用具有明确的健康益处,但与人类相比,BP 在兽医医学中的治疗功效的证据基础是有限的。尽管如此,BPs 在小动物兽医实践中被广泛用于治疗甲状旁腺功能亢进、猫的特发性高钙血症,以及缓解犬中常见的骨肿瘤的姑息治疗,特别是原发性骨肿瘤,如骨肉瘤。姑息性 BP 治疗最近在兽医肿瘤学中也有所增加,以缓解与肿瘤相关的骨痛。在马兽医实践中,非氮含 BPs 已获得 FDA 批准,用于控制成年马的跗关节综合征相关临床症状。然而,人们越来越担心 BPs 在幼年马中的非适应证使用。在这里,我们讨论了目前对兽医医学中 BP 使用的优势、劣势和当前争议的理解,以突出这些潜在有益药物的未来应用。