Alendronate, osteoporosis treatment

Osteoporosis (alendronate, risedronate, ibandronate) (alendronate/cholecalciferol treatment only) ... 

Treatment of osteoporosis depends on the cause. In secondary osteoporosis, treatment is directed at the underlying condition. Most therapies for the treatment of postmenopausal osteoporosis are directed at decreasing osteoclastic bone resorption. Antiresorptive therapies include bisphosphoiiates (alendronate and risedronate), estrogen replacement, selective estrogen receptor modulators (raloxifene), and calcitonin (nasal spray or injection). The FDA has recently approved recombinant hPTH(l-34) (injection), the first approved therapy for stimulating bone formation. 

Alendronate should be considered hrst-line treatment for primary osteoporosis in men owing to its proven benefit in reducing fractures and relative safety. 

Compared with postmenopausal osteoporosis, few clinical trials have been conducted evaluating therapies in men. Although alendronate and calcitonin have both been studied, only alendronate reduces fracture rates in men. Teriparatide also has been studied, but no data are available yet on fracture rates. At this time, alendronate and teriparatide are approved by the FDA for the treatment of osteoporosis in men. Owing to proven benefit in reducing fractures and relative safety, alendronate should be considered first-line treatment for primary osteoporosis in men. Teriparatide should be reserved as alternate therapy in this population. 

Alendronate, risedronate, and oral ibandronate are FDA approved for prevention and treatment of postmenopausal osteoporosis. IV ibandronate and zoledronic acid are indicated only for treatment of postmenopausal women. Risedronate and alendronate are also approved for male and glucocorticoid-induced osteoporosis. 

These results indicated osteoporosis. In this condition, which often appears secondary to another pathology such as an endocrinopathy, chronic renal failure or following long term immobilization, bone architecture is normal hut its mass is reduced relative to its volume, that is there is normal mineralization hut the amount of osteoid matrix is reduced. Treatment is with bone resorption inhibitors such as the bisphosphonate group of drugs, for example alendronate. 

Agents include etidronic acid, pamidronic acid, clodronic acid, alendronic acid, ibandronic acid, rise-dronic acid, zoledronic acid and tiludronic acid. Formulations of clodronic acid and pamidronic acid are available for intravenous administration. The indications for the use of bisphosphonates include treatment of postmenopausal osteoporosis, hypercal-caemia of malignancy and Paget s disease. 

Finally, bisphosphonates have an important place in treatment of osteoporosis of all causes, including steroid-induced osteoporosis. Disodium etidronate, alendronate and clodronate all have potent effects to restore bone mass, and this effect persists for several years of therapy. Newer drugs such as zoledronic acid can be administered by infrequent (once-yearly) infusion, which can help compliance and reduce side effects. 

Li, Chines and Meredith (2004) quote three clinical trials evaluating the effectiveness of alendronate, risedronate and raloxifene in increasing BMD and reducing fracture risk in osteoporosis. These treatments are seen to reduce fracture risk by similar amounts 47 per cent, 49 per cent and 46 per cent respectively, yet their effects on increasing BMD are somewhat different 6.2 per cent, 5.8 per cent and 2.7 per cent respectively. Drawing conclusions on the relative effectiveness of these treatments based solely in terms of the surrogate BMD would clearly be misleading. 

One would wish to see a side-by-side comparison of this and other routes and patterns of estrogen use before concluding whether there is indeed any dissociation of wanted and unwanted effects in view of current concern regarding estrogen use after the menopause, comparisons with non-hormonal treatment for osteoporosis (e.g. alendronate) would also be desirable. 

Turbi C, Herrero-Beaumont G, Acebes JC, Torrijos A, Grana J, Miguelez R, Sacristan JA, Marin F. Compliance and satisfaction with raloxifene versus alendronate for the treatment of postmenopausal osteoporosis in clinical practice an open-label, prospective, nonrandomized, observational study, din Ther 2004 26 245-56. 

General Category Bisphosphonates Examples Alendronate (Fosamax) Etidronate (Didronel) Ibandronate (Boniva) Pamidronate (Aredia) Risedronate (Actonel) Treatment Rationale and Principal Indications Appear to block excessive bone resorption and formation is used to normalize bone turnover in conditions such as osteoporosis and Paget disease, and to prevent hypercalcemia resulting from excessive bone resorption in certain forms of cancer... 

Bisphosphonates are potent inhibitors of bone resorption. They increase bone density and reduce the risk of fractures in the hip, spine, and other locations. Alendronate and risedronate are approved for the treatment of osteoporosis, using either daily dosing schedules alendronate 10 mg/d, risedronate 5 mg/d or weekly schedules alendronate 70 mg/wk, risedronate 35 mg/wk. These drugs are effective in men as well as women and for various causes of osteoporosis. 

Alendronate is licensed for the treatment of postmenopausal osteoporosis and osteoporosis in men, prevention of postmenopausal osteoporosis and the prevention and treatment of corticosteroid-induced osteoporosis. 

The benzothiophene derivative raloxifene (Evista /Lilly) is a selective estrogen receptor modulator (SERM). Raloxifene produces its biological actions via modulation (both activation and blockade) of estrogen receptors that ultimately results in decreased resorption of bone. The bisphosphonate derivative alendronate (Fosamax /Merck), an inhibitor of osteoclast-mediated bone resorption, is also useful in the treatment of osteoporosis. Both raloxifene and alendronate are useful in the treatment of osteoporosis in postmenopausal women. 

Uses. Three bisphosphonates (alendronate, etidronate, risedronate) are currently licensed in the UK for the treatment of osteoporosis (zoledronate is also effective), and the others are used in Paget s disease of bone, and hypercalcaemia due to cancer (pamidronate, clodronate, zoledronate). Bisphosphonates may also provide benefit for neoplastic disease that has spread to bone evidence indicates that clodronate by mouth and pamidronate i.v. are effective in the secondary prevention of bone metastases due to multiple myeloma and breast cancer. 

Alendronate is an aminobisphosphonate with general properties similar to those of the other bisphosphonates. It inhibits bone resorption and is nsed in osteoporosis and Paget s disease of bone. It has also been nsed in the treatment of bone metastases and hypercalcemia of malignancy. 

Bisphosphonates are widely used for the prevention and treatment of osteopenia and osteoporosis and for the reduction of skeletal complications in patients with malignant bone disease. Several oral bisphosphonates, including alendronate, risedronate, and ibandronate, are approved worldwide for the treatment of osteoporosis in postmenopausal women, as are intravenous (i.v.) formulations of ibandronate (3 mg quarterly) and zoledronic acid (5 mg annually). Several i.v. bisphosphonates are available for the treatment of the skeletal complications that frequently occur in malignant disease, such as hypercalcaemia of malignancy (HCM), multiple myeloma, and bone metastases associated with solid tumours. Pamidronate is approved worldwide for the treatment of HCM, multiple myeloma, and breast cancer bone metastases. Although not registered for oncology indications in the United States, i.v. ibandronate is widely available elsewhere for HCM and breast cancer bone metastases. 

Osteoporosis is of two forms- primary i.e. idiopathic and secondary. Primary osteoporosis is classified into type I and type II osteoporosis. Type I is referred to post menopausal osteoporosis which is the main type affecting women, characterized by rapid bone loss and affects women after the menopause, mainly in trabecular bone and is associated with vertebrae and distal radio fractures whereas type II also termed as senile osteoporosis occurs due to chronic deficiency of calcium, increase in parathormone activity and decrease in bone formation and is associated with aging. On the other hand secondary type results from inflammatory processes, endocrine changes, multiple myeloma, sedentariness and the use of drugs such as heparin, corticoid and alcohol [3]. Prevention is the main treatment of osteoporosis, for which bone mass peak and the prevention of postmenopausal reabsorption are critical elements. The common treatment of osteoporosis includes calcium consumption as calcium salts, vitamin D supplements, and hormone reposition [4], the use of calcitonin to modulate serum levels of calcium and phosphorous [5], the use of bisphosphonate, mainly alendronates [6], use of ipriflavone and sodium fluoride [7], besides physical activity to strengthen muscles, stimulate osteoblasts formation and prevent reabsorption. 

Lindsay R, Cosman F, Lobo RA, et al. Addition of alendronate to ongoing hormone replacement therapy in the treatment of osteoporosis A randomized controlled clinical trial. J Clin Endocrinol Metab 1999 84 3076-3081. 

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