***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: 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 Osteoporotic structural damage and bone fragility result from reduced bone formation and increased bone resorption . In a phase 2 clinical trial , strontium ranelate , an orally active drug that dissociates bone remodeling by increasing bone formation and decreasing bone resorption , has been shown to reduce the risk of vertebral fractures and to increase bone mineral density . METHODS To evaluate the efficacy of strontium ranelate in preventing vertebral fractures in a phase 3 trial , we r and omly assigned 1649 postmenopausal women with osteoporosis ( low bone mineral density ) and at least one vertebral fracture to receive 2 g of oral strontium ranelate per day or placebo for three years . We gave calcium and vitamin D supplements to both groups before and during the study . Vertebral radiographs were obtained annually , and measurements of bone mineral density were performed every six months . RESULTS New vertebral fractures occurred in fewer patients in the strontium ranelate group than in the placebo group , with a risk reduction of 49 percent in the first year of treatment and 41 percent during the three-year study period ( relative risk , 0.59 ; 95 percent confidence interval , 0.48 to 0.73 ) . Strontium ranelate increased bone mineral density at month 36 by 14.4 percent at the lumbar spine and 8.3 percent at the femoral neck ( P<0.001 for both comparisons ) . There were no significant differences between the groups in the incidence of serious adverse events . CONCLUSIONS Treatment of postmenopausal osteoporosis with strontium ranelate leads to early and sustained reductions in the risk of vertebral fractures UNLABELLED An 18-month r and omized double-blind study was conducted in postmenopausal women with osteoporosis to compare the effects of once-daily teriparatide 20 microg with alendronate 10 mg on bone histomorphometry . Biopsies were obtained from 42 patients .  Indices of bone formation were significantly higher after 6 or 18 months of teriparatide compared with alendronate treatment . INTRODUCTION Alendronate and teriparatide increased BMD , assessed by DXA , by different mechanisms of action , supported by changes in biochemical markers of bone turnover . The purpose of this cross-sectional study was to explore the differential effects of these two osteoporosis treatments at the bone tissue level by examining bone histomorphometric parameters of bone turnover after either 6 or 18 months of treatment . MATERIAL S AND METHODS Patients were a cohort from a r and omized parallel double-blind study conducted to compare the effects of once-daily teriparatide 20 microg and alendronate 10 mg in postmenopausal women with osteoporosis . Transiliac crest bone biopsies were obtained after tetracycline double labeling from 42 patients treated for 6 months ( n = 23 ) or 18 months ( n = 14 ) ; 5 additional patients were biopsied from contralateral sides at 6 and 18 months . Biopsy specimens adequate for quantitative analysis were analyzed by 2D histomorphometry from 17 patients at 6 months ( teriparatide , n = 8 ; alendronate , n = 9 ) and 15 patients at 18 months ( teriparatide , n = 8 ; alendronate , n = 7 ) . Data were analyzed by two- sample tests . RESULTS Histomorphometric indices of bone formation were significantly and markedly greater in the teriparatide group than in the alendronate group at 6 and 18 months , whereas indices of bone resorption were only significantly greater in the teriparatide group than in the alendronate group at 6 months . Bone formation and activation frequency were significantly lower at 18 months compared with 6 months in the teriparatide group , returning to levels comparable with untreated postmenopausal women . In the teriparatide group , the peak in histomorphometric bone formation indices coincided with peak levels for N-terminal propeptide of type I collagen , a biochemical marker of bone formation . The degree of mineralization was lower at 18 months than at 6 months with treatment in both groups but was not different between groups . CONCLUSIONS These results confirm the opposite mechanisms of action of teriparatide and alendronate on bone remodeling and confirm the bone formation effect of teriparatide Background A recent trial unexpectedly reported that atrial fibrillation , when defined as serious , occurred more often in participants r and omized to an annual infusion of the relatively new parenteral bisphosphonate , zoledronic acid , than among those given placebo , but had limited power . Two subsequent population -based case-control studies of patients receiving a more established oral bisphosphonate , alendronic acid  , reported conflicting results , possibly due to uncontrolled confounding factors . Methodology /Principal Findings We used the United Kingdom General Practice Research Data base to assess the  risk of atrial fibrillation and flutter in women exposed to the oral bisphosphonates , alendronic acid and risedronate sodium .  The self-controlled case-series method was used to minimise the potential for confounding . The age-adjusted incidence rate ratio for atrial fibrillation or flutter in individuals during their exposure to these oral bisphosphonates ( n = 2195 ) was 1.07 ( 95 % CI 0.94–1.21 ) . The age-adjusted incidence rate ratio for alendronic acid ( n = 1489 ) and risedronate sodium ( n = 649 ) exposed individuals were 1.09 ( 95 % CI 0.93–1.26 ) and 0.99 ( 95 % CI 0.78–1.26 ) respectively . In post-hoc analyses , an increased risk of incident atrial fibrillation or flutter was detected for patients during their first few months of alendronic acid therapy . Conclusions / Significance We found no robust evidence of an overall long-term increased risk of atrial fibrillation or flutter associated with continued exposure to the oral bisphosphonates , alendronic acid and risedronate sodium . A possible signal for an increase in risk during the first few months of therapy with alendronic acid needs to be re-assessed in additional studies Abstract Objective : To investigate changes in back pain in postmenopausal women with severe osteoporosis who received teriparatide for 24 months or switched at 12 months to raloxifene or no active treatment .  Study design and methods : This prospect i ve , controlled , r and omised , open-label , 2-year study enrolled 868 postmenopausal women with osteoporosis and a recent fragility fracture . After 12 months of teriparatide ( 20 µg/day ) , 507 patients were r and omised to further teriparatide ( n = 305 ) , raloxifene 60 mg/day ( n = 100 ) , or no active treatment ( n = 102 ) for another 12 months ( sub study 1 ) ; in sub study 2 , 199 patients continued teriparatide . All received calcium and vitamin D supplementation . Back pain was self-assessed by patients using a visual analogue scale ( 0–100 mm ) . Changes in back pain were analysed using a mixed model for repeated measures . Results : During year 1 , back pain decreased from a mean ( SD ) of 48.9 mm ( 24.0 ) at baseline by 11.5 mm ( p < 0.001 ) in the total study population . In sub study 1 , mean change in back pain from month 12 ( r and omisation ) to 24 months was −2.2 , −4.4 and + 0.7 mm in the teriparatide ( p = 0.076 ) , raloxifene ( p = 0.041 ) , and no active treatment groups ( p = 0.751 ) . There were no between-group differences from r and omization to 18 or 24 months . In a sensitivity analysis excluding patients with low baseline back pain ( VAS < 30 mm ) , mean change from r and omisation to endpoint was significant for teriparatide ( −3.9 mm , p = 0.006 ) and raloxifene ( −6.3 mm , p = 0.018 ) groups . Subgroup analyses of 503 patients who  received teriparatide for up to 2 years showed that patients with a recent vertebral fracture had a greater decrease in back pain than those without ( p < 0.05 ) . Those with and without mild back pain ( ≥30 mm ) , and those with and without severe back pain ( ≥60 mm ) at baseline all had a statistically significant reduction in back pain after 24 months ( p < 0.05 ) . Conclusions : Teriparatide treatment is associated with significant reductions in back pain regardless of the presence of recent vertebral fracture . These results need to be considered with caution due to the open-label design of the study Summary Vertebral fractures are a major adverse consequence of osteoporosis . In a large placebo-controlled trial in postmenopausal women with osteoporosis  , strontium ranelate reduced vertebral fracture risk by 33 % over 4 years , confirming the role of strontium ranelate as an effective long-term treatment in osteoporosis . Introduction Osteoporotic vertebral fractures are associated with increased mortality , morbidity , and loss of quality -of-life ( QoL ) . Strontium ranelate ( 2 g/day ) was shown to prevent bone loss , increase bone strength , and reduce vertebral and peripheral fractures . The preplanned aim of this study was to evaluate long-term efficacy and safety of strontium ranelate . 
    Output:
    
All the antiosteoporotic agents had significant efficacy in increasing lumbar spine bone mineral density and reduction in the occurrence of any new vertebral fractures .