Immobilization osteoporosis is found in a number of diseases, such as complete motor paralysis and reversible immobilization. In general, immobilization-induced mechanical loading declines in bones are known to be among the key factors of osteoporosis in spinal cord injury, stroke, and bed rest patients. However, recent research has also identified non-mechanical factors, including neural, endocrine, hormonal, nutritional, and iatrogenic factors. Prevention and treatment of immobilization osteoporosis can be divided into pharmacological and non-pharmacological methods. Pharmacologic treatments such as calcitonin, bisphosphonates, and oral phosphates have been applied to patients with spinal cord injury or under bed rest conditions to reduce bone loss. Recently, researchers have examined zoledronic acid, which has a positive impact on the prevention and treatment of acute stroke and spinal cord injury. Zoledronic acid is an intravenous bisphosphonate given once a year, thereby bypassing gastrointestinal absorption/irritation problems. However, several questions still remain, including whether bone loss should continue in immobilized patients with spinal cord injury or stroke, how long bone mineral density levels can remain intact after treatment, and how long the treatment should continue. As such, more extensive research that studies these questions in the long term is needed.