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Over the last two decades, bisphosphonate has widely been applied in the treatment of osteoporosis. We reviewed the various adverse effects, current trials involving diverse bone metabolic diseases, and the future direction of bisphosphonate. Acute phase reaction, hypocalcemia, ocular inflammation, and gastrointestinal disturbances are the well-known short-term side-effects of bisphosphonate. Long term side-effects include osteonecrosis of the jaws and atypical femur fracture. In the modern clinical setting, bisphosphonate is widely used in treatments for osteoporosis, osteopenia, osteoarthritis, rheumatoid arthritis, and metastatic bone cancer. Further studies are underway for expanding the application as a bone-targeting agent in bone-related diseases. Bisphosphonate remains useful and invaluable as the 1st line medication for osteoporosis. Considering the numerous clinical situations, including time to medication after fracture, duration of drug usage, and individual drug holiday, an optimal and proper use of bisphosphonate needs to be achieved. In the current scenario, bisphosphonate will retain a strong position due to good efficacy and effectiveness for osteoporosis treatment, and the precise application to various bone diseases. We anticipate a key role of bisphosphonate for future application in the treatment of metabolic bone diseases. Further studies and advancement are highly anticipated, considering the high potential of bisphosphonate for various uses.
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