***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Abstract : The purpose of this r and omized , double-masked , placebo-controlled study was to determine the efficacy and safety of risedronate in the prevention of vertebral fractures in postmenopausal women with established osteoporosis . The study was conducted at 80 study centers in Europe and Australia . Postmenopausal women ( n= 1226 ) with two or more prevalent vertebral fractures received risedronate 2.5 or 5 mg/day or placebo ; all subjects also received elemental calcium 1000 mg/day , and up to 500 IU/day vitamin D if baseline levels were low . The study duration was 3 years ; however , the 2.5 mg group was discontinued by protocol amendment after 2 years . Lateral spinal radiographs were taken annually for assessment of vertebral fractures , and bone mineral density was measured by dual-energy X-ray absorptiometry at 6-month intervals . Risedronate 5 mg reduced the risk of new vertebral fractures by 49 % over 3 years compared with control ( p<0.001 ) . A significant reduction of 61 % was seen within the first year ( p= 0.001 ) . The fracture reduction with risedronate 2.5 mg was similar to that in the 5 mg group over 2 years . The risk of nonvertebral fractures was reduced by 33 % compared with control over 3 years ( p= 0.06 ) . Risedronate significantly increased bone mineral density at the spine and hip within 6 months . The adverse-event profile of risedronate , including gastrointestinal adverse events , was similar to that of control . Risedronate 5 mg provides effective and well-tolerated therapy for severe postmenopausal osteoporosis , reducing the incidence of vertebral fractures and improving bone density in women with established disease UNLABELLED Oral daily ( 2.5 mg ) and intermittent ib and ronate ( between-dose interval of > 2 months ) , delivering a similar cumulative exposure , were evaluated in 2946 osteoporotic women with prevalent vertebral fracture . Significant reduction in incident vertebral fracture risk by 62 % and 50 % , respectively , was shown after 3 years . This is the first study to prospect ively show antifracture efficacy for the intermittent administration of a bisphosphonate . INTRODUCTION Bisphosphonates are important therapeutics in postmenopausal osteoporosis . However , they are currently associated with stringent dosing instructions that may impair patient compliance and hence therapeutic efficacy . Less frequent , intermittent administration may help to overcome these deficiencies . This study assessed the efficacy and safety of oral ib and ronate administered either daily or intermittently with a dose-free interval of > 2 months . MATERIAL S AND METHODS This r and omized , double-blind , placebo-controlled , parallel-group study enrolled 2946 postmenopausal women with a BMD T score < or = -2.0 at the lumbar spine in at least one vertebra ( L1-L4 ) and one to four prevalent vertebral fractures ( T4-L4 ) . Patients received placebo or oral ib and ronate administered either daily ( 2.5 mg ) or intermittently ( 20 mg every other day for 12 doses every 3 months ) . RESULTS AND CONCLUSIONS After 3 years , the rate of new vertebral fractures was significantly reduced in patients receiving oral daily ( 4.7 % ) and intermittent ib and ronate ( 4.9 % ) , relative to placebo ( 9.6 % ) . Thus , daily and intermittent oral ib and ronate significantly reduced the risk of new morphometric vertebral fractures by 62 % ( p = 0.0001 ) and 50 % ( p = 0.0006 ) , respectively , versus placebo . Both treatment groups also produced a statistically significant relative risk reduction in clinical vertebral fractures ( 49 % and 48 % for daily and intermittent ib and ronate , respectively ) . Significant and progressive increases in lumbar spine ( 6.5 % , 5.7 % , and 1.3 % for daily ib and ronate , intermittent ib and ronate , and placebo , respectively , at 3 years ) and hip BMD , normalization of bone turnover , and significantly less height loss than in the placebo group were also observed for both ib and ronate regimens . The overall population was at low risk for osteoporotic fractures . Consequently , the incidence of nonvertebral fractures was similar between the ib and ronate and placebo groups after 3 years ( 9.1 % , 8.9 % , and 8.2 % in the daily , intermittent , and placebo groups , respectively ; difference between arms not significant ) . However , findings from a posthoc analysis showed that the daily regimen reduces the risk of nonvertebral fractures ( 69 % ; p = 0.012 ) in a higher-risk subgroup ( femoral neck BMD T score < -3.0 ) . In addition , oral ib and ronate was well tolerated . Oral ib and ronate , whether administered daily or intermittently with an extended between-dose interval of > 2 months , is highly effective in reducing the incidence of osteoporotic fractures in postmenopausal women . This is the first time that significant fracture efficacy has been prospect ively shown with an intermittently administered bisphosphonate in the overall study population of a r and omized , controlled clinical trial . Thus , oral ib and ronate holds promise as an effective and convenient alternative to current bisphosphonate therapies BACKGROUND Risedronate increases bone mineral density in elderly women , but whether it prevents hip fracture is not known . METHODS We studied 5445 women 70 to 79 years old who had osteoporosis ( indicated by a T score for bone mineral density at the femoral neck that was more than 4 SD below the mean peak value in young adults [ -4 ] or lower than -3 plus a nonskeletal risk factor for hip fracture , such as poor gait or a propensity to fall ) and 3886 women at least 80 years old who had at least one nonskeletal risk factor for hip fracture or low bone mineral density at the femoral neck ( T score , lower than -4 or lower than -3 plus a hip-axis length of 11.1 cm or greater ) . The women were r and omly assigned to receive treatment with oral risedronate ( 2.5 or 5.0 mg daily ) or placebo for three years . The primary end point was the occurrence of hip fracture . RESULTS Overall , the incidence of hip fracture among all the women assigned to risedronate was 2.8 percent , as compared with 3.9 percent among those assigned to placebo ( relative risk , 0.7 ; 95 percent confidence interval , 0.6 to 0.9 ; P=0.02 ) . In the group of women with osteoporosis ( those 70 to 79 years old ) , the incidence of hip fracture among those assigned to risedronate was 1.9 percent , as compared with 3.2 percent among those assigned to placebo ( relative risk , 0.6 ; 95 percent confidence interval , 0.4 to 0.9 ; P=0.009 ) . In the group of women selected primarily on the basis of nonskeletal risk factors ( those at least 80 years of age ) , the incidence of hip fracture was 4.2 percent among those assigned to risedronate and 5.1 percent among those assigned to placebo ( P=0.35 ) . CONCLUSIONS Risedronate significantly reduces the risk of hip fracture among elderly women with confirmed osteoporosis but not among elderly women selected primarily on the basis of risk factors other than low bone mineral density Neridronate is a third generation bisphosphonate with established efficacy in metabolic bone disease . In this r and omized , open‐label study , 118 adults with β‐thalassaemia and bone mineral density ( BMD ) Z scores ≤−2·0 were r and omized 1:1–500 mg calcium with 400 international unis ( iu ) vitamin D daily or 500 mg calcium with 400 iu vitamin D daily plus neridronate 100 mg intravenously every 90 d. Significant increases in BMD at the lumbar spine and total hip were noted in the neridronate group at 6 and 12 months from baseline ( P < 0·001 ) , and values were significantly higher than the control group at both time  intervals . Neridronate also significantly decreased serum bone alkaline phosphatase and C‐telopeptide of collagen type 1 levels from as early as 3 months ( P = 0·04 and P < 0·001 , respectively ) , reaching significantly lower values at 12 months compared with the control group ( P < 0·05 ) . Reductions in back pain and analgesic use were also evident , starting 3 months from commencing treatment . Treatment was well tolerated by all patients . In this largest r and omized trial in thalassaemia‐induced osteoporosis to date , neridronate  was safe and effective in reducing bone resorption and increasing BMD . The associated reduction in back pain and improved quality of life will encourage adherence to therapy . ( Clinical trials.gov identifier NCT01140321 . UNLABELLED The efficacy of oral clodronate 800 mg daily to reduce vertebral fractures was studied in 593 women with postmenopausal or secondary osteoporosis . The incidence of vertebral fractures was significantly reduced by 46 % . The effect was not modified by the underlying cause of osteoporosis or other baseline factors including bone mineral density , QUS , weight , and smoking . INTRODUCTION This study aim ed to determine if the bisphosphonate , clodronate ( Bonefos ) , reduced the incidence of vertebral fractures in osteoporotic women . MATERIAL S AND METHODS Women fulfilling the WHO criteria for osteoporosis at the lumbar spine ( T-score < /= -2.5 ) and /or with at least one prevalent vertebral fracture were recruited to a 3-year double-blind , placebo-controlled study . A total of 593 patients were r and omized to two strata comprised of women with postmenopausal osteoporosis ( I , n = 483 ) and secondary osteoporosis ( II , n = 110 ) . They received either clodronate 800 mg daily orally ( n = 292 ) or an identical placebo ( n = 301 ) . All patients received a calcium supplement of 500 mg daily . BMD was measured at 6 , 12 , 24 , and 36 months , and lateral spine radiographs were obtained at baseline and annually thereafter for vertebral morphometry . RESULTS Treatment with clodronate was associated with a significant increase in mean spine BMD over 3 years ( percent change from baseline , 4.35 + /- 6.34 % versus 0.64 + /- 6.02 % in the placebo group , p < 0.0001 ) . At the hip , clodronate maintained total BMD , whereas a significant decrease was observed in the placebo group ( percent change from baseline 0.70 + /- 5.67 % versus -3.03 + /- 6.32 % in the placebo group , p < 0.0001 ) . The changes at the spine and hip were similar in both strata . Incident vertebral fractures at 3 years were observed in 63 women in the placebo group and 33 patients receiving clodronate ( relative risk , 0.54 ; 95 % CI , 0.37 - 0.80 ; p = 0.001 ) . Clodronate significantly reduced vertebral fracture risk in both strata and in women with or without prior vertebral fracture at baseline . Nonvertebral osteoporosis-associated fractures occurred in 21 women in the placebo group and in 14 women treated with clodronate . Treatment was well tolerated , with no significant difference in adverse event rates , including esophagitis , during clodronate treatment . CONCLUSION We conclude that clodronate 800 mg daily is a safe and effective treatment to reduce fracture risk in women with osteoporosis , regardless of causation Intravenous zoledronate 5 mg , administered annually , prevents fractures in people with osteoporosis , but the optimal dosing schedule is not known . Previously , we reported that a single dose of 5 mg zoledronate stably decreased bone turnover and increased bone mineral density ( BMD ) for 3 years in a r and omized controlled trial in 50 postmenopausal women with osteopenia . We have now completed a 2-year double-blind extension of this trial , during which no additional treatment was administered . The primary endpoint was change in the bone turnover markers procollagen type-I N-terminal propeptide ( P1NP ) and β-C-terminal telopeptide of type I collagen ( β-CTX ) ; the secondary endpoint was change in BMD at lumbar spine , total hip and total body . Mean levels of the each of the bone turnover markers were lower in the zoledronate group throughout the study ( P<0.0001 for each marker ) . After 5 years , mean ( 95 % CI ) levels of β-CTX and P1NP were 277 
    Output:
    
All bisphosphonates produced a significant decrease of the markers of bone turnover .
Alendronate , neridronate , and zoledronic acid significantly improved BMD at the lumbar spine , femoral neck and total hip .
Zoledronic acid and neridronate were also shown to reduce bone and back pain .
Sufficient evidence exists to support the use of bisphosphonates in the management of thalassemia-associated osteoporosis ( to prevent bone loss and improve the BMD ) .