***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: Context : Denosumab 60 mg sc injection every 6 months for 36 months was well tolerated and effective in reducing the incidence of vertebral , nonvertebral , and hip fracture in predominantly Caucasian postmenopausal women with osteoporosis . Objective : The objective of this phase 3 fracture study was to examine the antifracture efficacy and safety of denosumab 60 mg in Japanese women and men with osteoporosis compared with placebo . Design and Setting : A r and omized , double-blind , placebo-controlled trial with an open-label active comparator as a referential arm was conducted . Patients : Subjects were 1262 Japanese patients with osteoporosis aged 50 years or older , who had one to four prevalent vertebral fractures . Intervention : Subjects were r and omly assigned to receive denosumab 60 mg sc every 6 months ( n = 500 ) , placebo for denosumab ( n = 511 ) , or oral alendronate 35 mg weekly ( n = 251 ) . All subjects received daily supplements of calcium and vitamin D. Main Outcome Measure : The primary endpoint was the 24-month incidence of new or worsening vertebral fracture  for denosumab vs placebo . Results : Denosumab significantly reduced the risk of new or worsening vertebral fracture by 65.7 % , with incidences of 3.6 % in denosumab and 10.3 % in placebo at 24 months ( hazard ratio 0.343 ; 95 % confidence interval 0.194–0.606 , P = .0001 ) . No apparent difference in adverse events was found between denosumab and placebo during the first 24 months of the study . Conclusion : These results provide evidence of the efficacy and safety  of denosumab 60 mg sc every 6 months in Japanese subjects with osteoporosis CONTEXT Denosumab is an investigational fully human monoclonal antibody against receptor activator of nuclear factor-kappaB lig and , a mediator of osteoclastogenesis and osteoclast survival . OBJECTIVE This study evaluated the ability of denosumab to increase bone mineral density ( BMD ) and decrease bone turnover markers ( BTMs ) in early and later postmenopausal women with low BMD . DESIGN AND SETTING This 2-yr r and omized , double-blind , placebo-controlled study was conducted in North America . PARTICIPANTS Subjects included 332 postmenopausal women with lumbar spine BMD T-scores between -1.0 and -2.5 . INTERVENTIONS SUBJECTS were r and omly assigned to receive denosumab sc , 60 mg every 6 months , or placebo . R and omization was stratified by time since onset of menopause ( < or = 5 yr or > 5 yr ) . MAIN OUTCOME MEASURES The primary end point was the percent change in lumbar spine BMD by dual-energy x-ray absorptiometry at 24 months . Additional end points were percent change in volumetric BMD of the distal radius by quantitative computed tomography ; percent change in BMD by dual-energy x-ray absorptiometry for the total hip , one-third radius , and total body ; hip structural analysis ; percent change in BTMs ; and safety . RESULTS Denosumab significantly increased lumbar spine BMD , compared with placebo at 24 months ( 6.5 vs. -0.6 % ; P<0.0001 ) with similar results for both strata . Denosumab also produced significant increases in BMD at the total hip , one-third radius , and total body ( P < 0.0001 vs. placebo ) ; increased distal radius volumetric BMD ( P < 0.01 ) ; improved hip structural analysis parameters ; and significantly suppressed serum C-telopeptide , tartrate-resistant acid phosphatase-5b , and intact N-terminal propeptide of type 1 procollagen . The overall incidence of adverse events was similar between both study groups . CONCLUSIONS Twice-yearly denosumab increased BMD and decreased BTMs in early and later postmenopausal women CONTEXT For many patients , adhering to postmenopausal osteoporosis treatment is a challenge . Higher treatment satisfaction is associated with greater persistence with these therapies , which is associated with better outcomes . OBJECTIVE This study aim ed to evaluate the change in treatment satisfaction in postmenopausal women who were suboptimally adherent to daily or weekly oral bisphosphonates and who transitioned to denosumab vs a monthly oral bisphosphonate .  DESIGN AND SETTING Pooled data of out patients from two international , multicenter , r and omized , open-label studies were analyzed . PATIENTS Postmenopausal women ( n = 1703 ) age 55 years or greater with low bone mineral density who were suboptimally adherent with prior oral bisphosphonate therapy , as assessed by the Osteoporosis-Specific Morisky Medication Adherence Scale , were included in the study . INTERVENTIONS Patients received denosumab , a fully human monoclonal antibody to receptor activator of nuclear factor-kappa B lig and , 60 mg s.c . every 6 months vs the oral bisphosphonates ib and ronate or risedronate , 150 mg once monthly for 12 months . MAIN OUTCOME MEASURES Change in treatment satisfaction scores from baseline to months 6 and 12 were measured using the Treatment Satisfaction Question naire for Medication ( TSQM ) . The TSQM is a vali date d tool that measures perception of four domains of treatment satisfaction : effectiveness , side effects , convenience , and global satisfaction . RESULTS Patients in both treatment groups showed improvement from baseline for all four TSQM domains at 6 and 12 months . However , the denosumab group had significantly ( all P < .001 ) greater improvements among all four TSQM domains at 6 and 12 months compared with the oral bisphosphonate group . CONCLUSIONS Women with low adherence to oral bisphosphonates reported greater treatment satisfaction when transitioned to denosumab vs switching to a monthly oral bisphosphonate INTRODUCTION Denosumab is a fully human monoclonal antibody that inhibits receptor activator of nuclear factor-kappa B lig and ( RANKL ) , an essential mediator of osteoclast formation , function , and survival that has been shown to decrease bone turnover and increase bone mineral density ( BMD ) in treated patients . We assessed the long-term efficacy and safety of denosumab , and the effects of discontinuing and restarting denosumab treatment in postmenopausal women with low bone mass . METHODS Postmenopausal women with a lumbar spine T-score of -1.8 to -4.0 or proximal femur T-score of -1.8 to -3.5 were r and omized to denosumab  every 3 months ( Q3 M ; 6 , 14 , or 30 mg ) or every 6 months ( Q6 M ; 14 , 60 , 100 , or 210 mg ) ; placebo ; or open-label oral alendronate weekly . After 24 months , patients receiving denosumab either continued treatment at 60 mg Q6 M for an additional 24 months , discontinued therapy , or discontinued treatment for 12 months then re-initiated denosumab ( 60 mg Q6 M ) for 12 months . The placebo cohort was maintained . Alendronate-treated patients discontinued alendronate and were followed . Changes in BMD and bone turnover markers ( BTM ) as well as safety outcomes were evaluated . RESULTS Overall , 262/412 ( 64 % ) patients completed 48 months of study . Continuous , long-term denosumab treatment increased BMD at the lumbar spine ( 9.4 % to 11.8 % ) and total hip ( 4.0 % to 6.1 % ) . BTM were consistently suppressed over 48 months . Discontinuation of denosumab was associated with a BMD decrease of 6.6 % at the lumbar spine and 5.3 % at the total hip within the first 12 months of treatment discontinuation . Retreatment with denosumab  increased lumbar spine BMD by 9.0 % from original baseline values . Levels of BTM increased upon discontinuation and decreased with retreatment . Adverse event rates were similar among treatment groups . CONCLUSIONS In postmenopausal women with low BMD , long-term denosumab treatment led to gains in BMD and reduction of BTM throughout the course of the study . The effects on bone turnover were fully reversible with discontinuation and restored with subsequent retreatment OBJECTIVE : To compare the efficacy and safety of denosumab to ib and ronate in postmenopausal women with low bone mineral density ( BMD ) previously treated with a bisphosphonate . METHODS : In a r and omized , open-label study , postmenopausal women received 60 mg denosumab subcutaneously every 6 months ( n=417 ) or 150 mg ib and ronate orally every month ( n=416 ) for 12 months . End points included percentage change from baseline in total hip , femoral neck , and lumbar spine BMD at month 12 and percentage change from baseline in serum C-telopeptide at months 1 and 6 in a sub study . RESULTS : At month 12 , significantly greater BMD gains from baseline were observed with denosumab compared with ib and ronate at the total hip ( 2.3 % compared with 1.1 % ) , femoral neck ( 1.7 % compared with 0.7 % ) , and lumbar spine ( 4.1 % compared with 2.0 % ; treatment difference P<.001 at all sites ) . At month 1 , median change in serum C-telopeptide from baseline was −81.1 % with denosumab and –35.0 % with ib and ronate ( P<.001 ) ; the treatment difference remained significant at month 6 ( P<.001 ) . Adverse events occurred in 245 ( 59.6 % ) denosumab-treated women and 230 ( 56.1 % ) ib and ronate-treated women ( P=.635 ) . The incidence of serious adverse events was 9.5 % for denosumab-treated women and 5.4 % for ib and ronate-treated women ( P=.046 ) . No clustering of events in any organ system accounted for the preponderance of these reports . The incidence rates of serious adverse events involving infection and malignancy were similar between treatment groups . CONCLUSION : In postmenopausal women previously treated with a bisphosphonate and low BMD  , denosumab treatment result ed in greater BMD  increases than ib and ronate at all measured sites . No new safety risks with denosumab treatment were identified . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00936897 . LEVEL OF EVIDENCE : BACKGROUND Receptor activator of nuclear factor-kappaB lig and ( RANKL ) is essential for osteoclast differentiation , activation , and survival . The fully human monoclonal antibody denosumab ( formerly known as AMG 162 ) binds RANKL with high affinity and specificity and inhibits RANKL action . METHODS The efficacy and safety of subcutaneously administered denosumab were evaluated over a period of 12 months in 412 postmenopausal women with low bone mineral density ( T score of -1.8 to -4.0 at the lumbar spine or -1.8 to -3.5 at the proximal femur ) . Subjects were r and omly assigned to receive denosumab either every three months ( at a dose of 6 , 14 , or 30 mg ) or every six months ( at a dose of 14 , 60 , 100 , or 210 mg ) , open-label oral alendronate once weekly ( at a dose of 70 mg ) , or placebo . The primary end point was the percentage change from baseline in bone mineral density at the lumbar spine at 12 months . Changes in bone turnover were assessed by measurement of serum and urine telopeptides and bone-specific alkaline phosphatase . RESULTS Denosumab treatment for 12 months result ed in an increase in bone mineral density at the lumbar spine of 3.0 to 6.7 percent ( as compared with an increase of 4.6 percent with alendronate and a loss of 0.8 percent with placebo ) , at the total hip of 1.9 to 3.6 percent ( as compared with an increase of 2.1 percent with alendronate and a loss of 0.6 percent with placebo ) , and at the distal third of the radius of 0.4 to 1.3 percent ( as compared with decreases of 0.5 percent with alendronate and 2.0 percent with placebo ) . Near-maximal reductions in mean levels of serum C-telopeptide from baseline were evident three days after the administration of denosumab . The duration of the suppression of bone turnover appeared to be dose-dependent . CONCLUSIONS In postmenopausal women with low bone mass , denosumab increased bone mineral density and decreased bone resorption . These preliminary data suggest that denosumab might be an effective treatment for osteoporosis . ( Clinical Trials.gov number , NCT 
    Output:
    
CONCLUSION Denosumab can be used both as a first-line agent and an alternative to bisphosphonate in the treatment of postmenopausal osteoporosis .
There is currently insufficient data to show that denosumab is not inferior to bisphosphonates in fracture prevention