***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 
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    ***EXAMPLES*** 
    Input: To confirm the inhibitory effect of etidronate on the progression of vascular calcification ( VC ) , 21 patients were r and omly enrolled . All 21 patients had end-stage renal disease and were undergoing hemodialysis ( HD ) three times per week . Patients were observed clinical ly for 12 months before etidronate treatment and then etidronate was given orally just prior to sleep on the days of dialysis for 23 months . The aortic calcification area ( ACA ) increased significantly during the 12 months before etidronate treatment . While the ACA of the drug-treated group did not change 12 and 23 months after the initiation of etidronate treatment , the ACA in the control group was significantly elevated 23 months later . These results strongly indicate that etidronate inhibits the progression of VC . Bone mineral density did not change during etidronate treatment . Our findings suggest that etidronate might effectively protect against progressive VC in HD patients BACKGROUND Vitamin D deficiency may be involved in the development of atherosclerosis and coronary heart disease in humans . METHODS We assessed prospect ively whether plasma 25-hydroxyvitamin D ( 25[OH]D ) concentrations are associated with risk of coronary heart disease . A nested case-control study was conducted in 18,225 men in the Health Professionals Follow-up Study ; the men were aged 40 to 75 years and were free of diagnosed cardiovascular disease at blood collection . The blood sample s were returned between April 1 , 1993 , and November 30 , 1999 ; 99 % were received between April 1 , 1993 , and November 30 , 1995 . During 10 years of follow-up , 454 men developed nonfatal myocardial infa rct ion or fatal coronary heart disease . Using risk set sampling , controls ( n = 900 ) were selected in a 2:1 ratio and matched for age , date of blood collection , and smoking status . RESULTS After adjustment for matched variables , men deficient in 25(OH)D ( < or=15 ng/mL [ to convert to nanomoles per liter , multiply by 2.496 ] ) were at increased risk for MI compared with those considered to be sufficient in 25(OH)D ( > or=30 ng/mL ) ( relative risk [ RR ] , 2.42 ; 95 % confidence interval [ CI ] , 1.53 - 3.84 ; P < .001 for trend ) . After additional adjustment for family history of myocardial infa rct ion , body mass index , alcohol consumption , physical activity , history of diabetes mellitus and hypertension , ethnicity , region , marine omega-3 intake , low- and high-density lipoprotein cholesterol levels , and triglyceride levels , this relationship remained significant ( RR , 2.09 ; 95 % CI , 1.24 - 3.54 ; P = .02 for trend ) . Even men with intermediate 25(OH)D levels were at elevated risk relative to those with sufficient 25(OH)D levels ( 22.6 - 29.9 ng/mL : RR , 1.60 [ 95 % CI , 1.10 - 2.32 ] ; and 15.0 - 22.5 ng/mL : RR , 1.43 [ 95 % CI , 0.96 - 2.13 ] , respectively ) . CONCLUSION Low levels of 25(OH)D are associated with higher risk of myocardial infa rct ion in a grade d manner , even after controlling for factors known to be associated with coronary artery disease Background —Osteoprotegerin is a novel member of the tumor necrosis factor receptor superfamily and a soluble decoy receptor of the receptor activator of nuclear factor-κB lig and . Recent experimental research has implicated osteoprotegerin in atherogenesis , but epidemiological confirmation of this concept is sparse . Methods and Results —As part of the prospect i ve , population -based Bruneck Study , severity , initiation , and progression of atherosclerosis were assessed in carotid arteries . Cases of incident cardiovascular disease and vascular mortality  were carefully recorded over a 10-year period ( 1990 to 2000 )  . Osteoprotegerin levels  were measured in sample s obtained at baseline and during follow-up . Serum osteoprotegerin  showed a strong association with numerous vascular risk factors , including age , diabetes , markers of systemic inflammation , chronic infection , and smoking . In multivariate analyses , osteoprotegerin was significantly related to severity and 10-year progression of carotid atherosclerosis . Furthermore , a high level of osteoprotegerin was an independent risk factor for incident cardiovascular disease ( adjusted relative risk for the top versus bottom tertile group for osteoprotegerin 2.2 [ 1.3 to 3.8 ] ; P = 0.001 ) and vascular mortality ( adjusted relative risk for the top versus bottom tertile group for osteoprotegerin 3.1 [ 1.2 to 8.2 ] ; P = 0.010 ) but not for mortality due to nonvascular causes . Conclusions —Osteoprotegerin is an independent risk factor for the progression of atherosclerosis and onset of cardiovascular disease Animal experiments revealed conflicting results as to the impact of bisphosphonate treatment on atherosclerosis and related vascular calcification . The effect of long-term treatment with clinical doses of bisphosphonates on aortic calcification ( AC ) in an “ at-risk ” population of osteoporotic elderly women has not been assessed systematic ally . In the present analysis including 474 women ( 55–80 years ) participating in two 3-year r and omized , placebo-controlled clinical trials , we assessed the simultaneous impact of ib and ronate given either orally ( 2.5 mg daily or 20 mg intermittently ) or intravenously ( 0.5 mg or 1.0 mg IV every 3 months ) on bone mass and AC . All women received calcium and vitamin D supplements .  Bone mineral density ( BMD ) was measured at the lumbar spine and the total hip using dual-energy X-ray absorptiometry ( DXA ) . Calcified deposits of the lumbar aorta ( L1–L4 ) were visualized on lateral radiographs and severity was grade d by a vali date d scoring system . Measurements were performed at baseline and at years 1 , 2 , and 3 . At baseline , there was a significant inverse correlation between the severity of AC and BMD at the hip ( r=−0.151 , P=0.003 ) , but not at the lumbar spine . The two oral doses and the 1.0 mg IV dose evoked statistically significant increases in both hip and spine BMD compared with placebo , whereas the effect of 0.5 mg was significant only at the hip ( P<0.05 ) . No differences in the yearly rate of progression or the 3-year change in AC was observed between the different intervention groups . Furthermore , there were no statistically significant correlations between the 3-year change in BMD and the simultaneous change in AC . These findings thus suggest that 3-year treatment with effective doses of ib and ronate does not pose any cardiovascular risk in terms of altering vascular calcification Kidney transplant recipients develop secondary osteoporosis induced by immunosuppressive medication , with a high risk of fracture , and abdominal aortic calcification ( AC ) is a known predictor of cardiovascular mortality . In this study of 12 stable kidney recipients , we estimated the preventive effect of bisphosphonate treatment on bone loss and progression of AC . We r and omly divided the subjects into a treatment group with alendronate ( group A : 5 subjects ) and a control group ( group C : 7 subjects ) . Group A patients received 35 mg/week of alendronate over 24 months , while group C patients were not administered with any bisphosphonates . Two major endpoints were established : ( 1 ) the time-dependent change in bone mineral density ( BMD ) estimated with DEXA and ( 2 ) progression of abdominal AC , calculated twice as an index ( ACI ) using computed tomography data . Over the 2-year study period , group A patients showed significantly increased BMD of 1.86 ± 0.85 % ( P = 0.015 versus baseline ) , and almost complete inhibition of ACI progression ( 38.2 ± 24.2 % to 39.6 ± 24.3 % ) , but group C patients showed a decrease in BMD decline with bone loss and progression of ACI ( 32.8 ± 25.0 % to 37.8 ± 29.2 % , P = 0.061 ) . In conclusion , alendronate therapy was an effective treatment in kidney transplant recipients for secondary osteoporosis and vascular calcification as ectopic calcification . This clinical trial is registered with number JMA-IIA00155 of JMACCT CTR BACKGROUND : Mortality is increased after a hip fracture , and strategies that improve outcomes are needed . METHODS : In this r and omized , double-blind , placebo-controlled trial , 1065 patients were assigned to receive yearly intravenous zoledronic acid  ( at a dose of 5 mg ) , and 1062 patients were assigned to receive placebo .  The infusions were first administered within 90 days after surgical repair of a hip fracture . All patients received supplemental vitamin D and calcium . The median follow-up was 1.9 years . The primary end point was a new clinical fracture . RESULTS : The rates of any new clinical fracture were 8.6 % in the zoledronic acid group and 13.9 % in the placebo group , a 35 % risk reduction ( P = 0.001 ) ; the respective rates of a new clinical vertebral fracture were 1.7 % and 3.8 % ( P = 0.02 ) , and the respective rates of new nonvertebral fractures were 7.6 % and 10.7 % ( P = 0.03 ) . In the safety analysis , 101 of 1054 patients in the zoledronic acid group ( 9.6 % ) and 141 of 1057 patients in the placebo group ( 13.3 % ) died , a reduction of 28 % in deaths from any cause in the zoledronic-acid group ( P = 0.01 ) . The most frequent adverse events in patients receiving zoledronic acid were pyrexia , myalgia , and bone and musculoskeletal pain . No cases of osteonecrosis of the jaw were reported , and no adverse effects on the healing of fractures were noted . The rates of renal and cardiovascular adverse events , including atrial fibrillation and stroke , were similar in the two groups . CONCLUSIONS : An annual infusion of zoledronic acid within 90 days after repair of a low-trauma hip fracture was associated with a reduction in the rate of new clinical fractures and improved survival . ( Clinical Trials.gov number , NCT00046254 . ) OBJECTIVE Osteoporosis and atherosclerosis are interconnected entities and share also some pathophysiological mechanisms . Moreover , recent literature data have supported the hypothesis that bisphosphonates ( BPs ) may have some antiatherogenic actions . This study aim ed to evaluate the effects of one year with zoledronate or ib and ronate given intravenously on lipid profile and on carotid artery intima-media thickness ( CA-IMT ) . METHODS Sixty postmenopausal osteoporotic women ( mean age : 66.6±7.8years ) were r and omly assigned to 1-year treatment with zoledronate 5 mg i.v . annually or ib and ronate 3 mg i.v . every 3 months . In all patients at baseline and after 12months we measured CA-IMT , total cholesterol ( TC ) , high-density lipoprotein cholesterol ( HDL-C ) , low-density lipoprotein cholesterol ( LDL-C ) , 25-hydroxyvitamin D ( 25OHD ) , bone alkaline phosphatase ( B-ALP ) , type I collagen β carboxy telopeptide ( βCTX ) , osteocalcin ( OC ) , fibroblast growth factor 23 ( FGF-23 ) and sclerostin . RESULTS The osteoporotic women treated with zoledronate showed a greater reduction in CA-IMT than those treated with ib and  ronate . HDL-C and HDL-C/LDL-C ratio showed a significant ( p<0.01 ) increase in the 2 groups , whereas , LDL-C showed a reduction in the two groups which , however , reached statistical significance ( p<0.05 ) only in the zoledronate group . FGF-23 serum levels showed a similar and significant decrease in both the women treated with zoledronate and in those treated with ib and ronate . At the end of the study period sclerostin serum levels showed a higher increase in the patients treated with zoledronate than in those treated with ib and ronate . CONCLUSION In osteoporotic women  both zoledronate and ib and ronate given intravenously result ed in an increase in HDL-C/LDL-C ratio and a reduction of CA-IMT which was significant only for zoledronate . Further prospect 
    Output:
    
Results In several studies , etidronate limited the progression of aortic and coronary calcification in hemodialysis patients , whereas the nitrogen-containing-BPs given orally did not significantly reduce vascular calcifications in patients with chronic kidney disease , kidney trasplant or in those with osteoporosis .
Nitrogen-containing-BPs present favorable effects both on vessel wall thickness and on arterial elasticity due to both a reduction in serum lipids and the interaction of BPs with the bone tissue , with the consequent release of bone turnover markers and cytokines into the bloodstream .