***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: 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 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 The purpose of this study was to evaluate the efficacy of calcitonin on β-endorphin levels in female patients experiencing back pain associated with postmenopausal osteoporosis . The secondary purpose was to assess the pain and quality of life in these patients . There were 30 patients with a mean age of 58.2±5.4 years in the treatment group and 26 patients with a mean age of 58.8±5.2 years in the placebo group in this r and omized , placebo-controlled study . The patients subcutaneously received 100 IU salmon calcitonin or placebo injections and 1,000 mg elementary calcium for 2 weeks . Baseline plasma β-endorphin levels were measured and repeated after 2 weeks . Patients ’ pain and quality of life ( QOL ) were evaluated by using the Visual Analogue Scale , Modified Face Scale , Beck Depression Index , and Nottingham Health Profile . Patients ’ global assessment of disease activity was also performed at baseline and at the end of the first and second week . We found that plasma β-endorphin levels in the treatment group were significantly higher than the placebo group at the end of the second week ( p<0.001 ) . Although pain and QOL scores were improved at the end of the second week in both groups ( p<0.05 ) , the improvement in the treatment group was more significant when compared with the placebo group ( p<0.05 ) . Therefore , calcitonin is an analgesic agent , as it increases the plasma β-endorphin levels in patients with postmenopausal osteoporosis , which consequently improves QOL Objective : To compare the efficacy and tolerability of once-weekly ( OW ) alendronate ( ALN ) 70 mg and raloxifene ( RLX ) 60 mg daily in the treatment of postmenopausal osteoporosis . Design : This 12-month , r and omized , double-blind study enrolled 456 postmenopausal women with osteoporosis ( 223 ALN , 233 RLX ) at 52 sites in the United States . Efficacy measurements included lumbar spine ( LS ) , total hip , and trochanter bone mineral density ( BMD ) at 6 and 12 months , biochemical markers of bone turnover , and percent of women who maintained or gained BMD in response to treatment . The primary endpoint was percent change from baseline in LS BMD at 12 months . Adverse experiences were recorded to assess treatment safety and tolerability . Results : Over 12 months , OW ALN produced a significantly greater increase in LS BMD ( 4.4 % , P < 0.001 ) than RLX ( 1.9 % ) . The percentage of women with ≥ 0 % increase in LS BMD ( ALN , 94 % ; RLX , 75 % ; P < 0.001 ) and ≥ 3 % increase in LS BMD ( ALN , 66 % ; RLX , 38 % ; P < 0.001 ) were significantly greater with ALN than RLX . Total hip and trochanter BMD increases were also significantly greater ( P ≤0.001 ) with ALN . Greater ( P < 0.001 ) reductions in N-telopeptide of type I collagen and bone-specific alkaline phosphatase were achieved with ALN compared with RLX at 6 and 12 months . No significant differences in the incidence of upper gastrointestinal or vasomotor adverse experiences were seen . Conclusion : ALN 70 mg OW produced significantly greater increases in spine and hip BMD and greater reductions in markers of bone turnover  than RLX over 12 months . A greater percentage of women maintained or gained BMD on ALN than RLX . Both medications had similar safety and tolerability profiles Less frequent bisphosphonate dosing in women with postmenopausal osteoporosis has the potential to promote therapy adherence through improved convenience . Ib and ronate is a highly potent nitrogen-containing bisphosphonate , proven to significantly increase vertebral and nonvertebral bone mineral density ( BMD ) when administered as a convenient intravenous injection . A recent double-blind , placebo-controlled , r and omized phase III study explored the antifracture efficacy and safety of 1 and 0.5 mg iv ib and ronate injections , given once every 3 months , in 2862 women ( 55 - 76 years ) with postmenopausal osteoporosis [ one to four prevalent vertebral fractures and lumbar spine ( L1-L4 ) BMD T score of less than -2.0 and greater than -5.0 in > or=1 vertebra ] . All participants received daily vitamin D ( 400 IU ) and calcium ( 500 mg ) supplementation . The primary endpoint was the incidence of new morphometric vertebral fractures after 3 years . However , although a consistent trend toward a reduction in the incidence of new morphometric vertebral fracture was observed in the active treatment arms compared with placebo ( 9.2 % vs. 8.7 % vs. 10.7 % in the 1 mg , 0.5 mg and placebo groups , respectively ) , as well as in the incidence of nonvertebral and hip fractures , the magnitude of fracture reduction was suboptimal and was insufficient to achieve statistical significance . At the studied doses , intravenous ib and ronate injections also produced dose-dependent , but comparatively small , increases in lumbar spine BMD ( 4.0 % and 2.9 % , respectively ) and decreases in biochemical markers of bone resorption and formation , relative to placebo .  Optimal fracture efficacy likely requires more substantial increases in BMD and more pronounced suppression of bone turnover . In light of the clear dose-response relationship observed in this and other studies , this is likely to be achieved with higher intravenous doses of ib and ronate . The results of a recent phase II/III study ( Intermittent Regimen Intravenous Ib and ronate Study : the IRIS study ) provide support for this hypothesis This study evaluated the efficacy and tolerability of risedronate once a week ( 35 mg and 50 mg ) compared with risedronate 5 mg once daily in women with osteoporosis . We conducted a r and omized , double-blind , active-controlled , 2-year study ; the primary efficacy assessment was performed after 1 year . Subjects were women aged 50 years or older who had been postmenopausal for at least 5 years , with either a bone mineral density ( BMD ) T-score of -2.5 or lower ( lumbar spine or proximal femur ) or a T-score lower than -2 and at least one prevalent vertebral fracture . Subjects received risedronate 5 mg once daily , 35 mg once a week or 50 mg once a week . All subjects also received 1 g daily of elemental calcium supplementation and supplemental vitamin D if the baseline serum levels were low . The primary efficacy measure was percent change in lumbar spine BMD at 12 months . A total of 1,456 women were r and omized and received medication ; 1,209 ( 83 % ) women completed 12 months . The mean percent change ( SE ) in lumbar spine BMD after 12 months was 4.0 % ( 0.2 % ) in the 5 mg daily group , 3.9 % ( 0.2 % ) in the 35 mg group , and 4.2 % ( 0.2 % ) in the 50 mg group ; each once-a-week treatment was determined to be as effective as the daily treatment . Outcomes of the secondary efficacy measurements and safety assessment s were also similar in all 3 groups after 12 months . Risedronate 35 mg and 50 mg once a week provide the same efficacy and safety as the daily 5 mg regimen ; therefore , the lower dose , 35 mg once a week , is considered optimal for women with postmenopausal osteoporosis who desire a once-a-week regimen Adherence to oral daily bisphosphonate regimens in postmenopausal osteoporosis is currently suboptimal . Less frequent dosing regimens are likely to improve patient adherence and thus , potentially , patient outcomes . A multicenter , r and omized , double-blind , noninferiority study was conducted in 235 women ( 53 - 80 yr old ; time since menopause > /== " BORDER="0 " > 3 yr ) with postmenopausal osteoporosis [ lumbar spine ( L1-L4 ) bone mineral density ( BMD ) T-score < /= -2 ] to demonstrate the noninferiority of an oral weekly ( 20 mg ) ib and ronate regimen compared with an oral daily ( 2.5 mg ) ib and ronate regimen . All patients received daily calcium ( 500 mg ) and vitamin D ( 400 IU ) . The primary analysis was the relative change in lumbar 
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Bisphosphonates were reported to have consistently reduced the risk of vertebral fractures .
Hormone replacement therapy showed positive outcomes , but its use has been found to increase the risk of cardiovascular disease and breast cancer .
Teriparatide and monofluorophosphate also showed efficacy against osteoporosis .