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Bisphosphonates are effective in decreasing bone resorption, the incidence of fragility fracure, and pain from bone metastases. Although relatively well tolerated, the initial dose(s)of intravenous or oral monthly aminobisphosphonates can be associated with an acute phase response, a nonspecific physiologic reaction associated with increased levels of inflammatory cytokines, fever, and flu like symptoms including fatigue, nausea, and myalgia within 3 days of dosing and lasting 7 days or less. Nitrogen-BPs(N-BPs)inhibit osteoclast function by acting as potent inhibitors of the enzyme farnesyl diphosphate(FPP)synthase in the mevalonate biosynthetic pathway. Following an intravenous infusion or oral monthly BPs, transient uptake of N-BP into peripheral blood monocytes results in intracellular accumulation of isopentenyl diphosphate(IPP)due to FPP synthase inhibition. Recognition of IPP by γδT cells triggers their activation and expansion, resulting in the release of pro-inflammatory cytokines that cause the flulike symptoms of the acute phase reaction. There is trial evidence that its severity can be reduced by more than half with coadministration of acetaminophen, so the short-term use of these drugs to lessen the APR is advisable in patients receiving their first dosing of N-BPs. Levels of 25(OH)D were negatively correlated with the incidence and severity of APR. Vitamin D reduces the intensity of musculoskeletal pain after dosing of N-BPs for postmenopausal osteoporosis. APR has minimal impact on long-term adherence to therapy. It is less common in subjects who have previously used bisphosphonates. Information of APR to a patient is important before administration.

Paget's disease is a localized and progressive disorder of bone, characterized by increased bone remodeling. The increase of bone turnover changed bone quality in Paget's disease. The assessment of bone quality is consisted on two properties of structure and material. Bone quality is evaluated clinically by the bone turnover. Treatment of bisphosphonate in Paget's disease controlled bone turnover. There's a possibility that treatment of bisphosphonate improve not only the property of structure but also that of material. It's hoped that the newer and stronger bisphosphonates play an increasingly important role in the treatment for bone quality of Paget's disease.

Patients with rheumatoid arthritis (RA) develop both generalized and periarticular osteoporosis. Osteoporosis in RA causes by increase of bone resorption, however the decrease of bone formation has been concerned in development of osteoporosis. Drug therapy have to bigin as early as osteopenia, and a potent inhibitor of bone resorption will be effective to suppress the increse of bone resorption in RA patients. RA-associated osteoporosis including grucocorticoid induced osteoporosis decreases bone formation, vitamin D and parathyroid hormon would become the useful drug for promoting the bone formation by examination of new agents, method and dosage of treatment for osteoporosis in RA patients.