human
***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 —Low 25-hydroxyvitamin D levels , commonly found in older patients with heart failure , may contribute to the chronic inflammation and skeletal myopathy that lead to poor exercise tolerance . We tested whether vitamin D supplementation of patients with heart failure and vitamin D insufficiency can improve physical function and quality of life . Methods and Results —In a r and omized , parallel group , double-blind , placebo-controlled trial , patients with systolic heart failure aged ≥70 years with 25-hydroxyvitamin D levels < 50 nmol/L ( 20 ng/mL ) received 100000 U of oral vitamin D2 or placebo at baseline and 10 weeks . Outcomes measured at baseline , 10 weeks , and 20 weeks were 6-minute walk distance , quality of life ( Minnesota score ) , daily activity measured by accelerometry , Functional Limitations Profile , B-type natriuretic peptide , and tumor necrosis factor-&agr;. Participants in the vitamin D group had an increase in their 25-hydroxyvitamin D levels compared with placebo at 10 weeks ( 22.9 versus 2.3 nmol/L [ 9.2 versus 0.9 ng/mL ] ; P<0.001 ) and maintained this increase at 20 weeks . The 6-minute walk did not improve in the treatment group relative to placebo . No significant benefit was seen on timed up and go testing , subjective measures of function , daily activity , or tumor necrosis factor . Quality of life worsened by a small , but significant amount in the treatment group relative to placebo . B-type natriuretic peptide decreased in the treatment group relative to placebo ( −22 versus + 78 pg/mL at 10 weeks ; P=0.04 ) . Conclusions —Vitamin D supplementation did not improve functional capacity or quality of life in older patients with heart failure with vitamin D insufficiency . Clinical Trial Registration —www.controlled-trials.com . Identifier : IS RCT N51372896 Background In meta-analyses supplementation with vitamin D appears to reduce incidence of fractures , and in cross-sectional studies there is a positive association between serum 25-hydroxyvitamin D ( 25(OH)D ) levels and bone mineral density ( BMD ) . However , the effect of supplementation with high doses of vitamin D on BMD is more uncertain and could in theory have both positive and negative effects . Methods The study was a one year , double blind placebo-controlled intervention trial performed at the University Hospital of North Norway . 421 subjects , 21 - 70 years old , were included and 312 completed the study . The subjects were r and omized to vitamin D3 40.000 IU per week ( DD group ) , vitamin D3 20.000 IU per week ( DP group ) , or placebo ( PP group ) . All subjects were given 500 mg calcium daily . Serum 25(OH)D , osteoprotegrin ( OPG ) , receptoractivator of nuclear factor-kappaB lig and ( RANKL ) , and BMD at the lumbar spine and the hip were measured before and at the end of the study . Results At baseline the mean serum 25(OH)D levels were 58 nmol/L ( all subjects ) and increased to 141 and 100 nmol/L in the DD and DP groups , respectively . After one year , no significant differences were found between the three groups regarding change in BMD , serum OPG or RANKL . Conclusions Supplementation with high doses of vitamin D for one year does not appear to have a negative effect on  BMD in healthy subjects . In order to disclose a positive effect , subjects with low BMD and /or low serum 25(OH)D levels need to be studied . Trial registration The trial was registered at Clinical Trials.gov ( NCT00243256 ) OBJECTIVES To assess the feasibility of a vitamin D intervention delivered through a Meals-on-Wheels ( MOW ) program to improve 25-hydroxyvitamin D ( 25(OH)D ) concentrations and reduce falls in homebound older adults . DESIGN Single-blind , cluster r and omized trial . SETTING MOW , Forsyth County , North Carolina . PARTICIPANTS Community-dwelling homebound adults aged 65 to 102 ( N = 68 ) . INTERVENTION MOW clients were r and omized to vitamin D3 ( 100,000 IU/month ; n = 38 ) or active placebo ( 400 IU vitamin E/month ; n = 30 ) according to MOW delivery route . MEASUREMENTS Serum 25(OH)D was assessed at baseline and 5-month follow-up ; proportions of participants in 25(OH)D categories were compared using Fisher exact test . Falls were assessed using monthly fall calendars , and rate of falls was estimated using negative binomial generalized estimating equation models . RESULTS Mean ± st and ard deviation 25(OH)D concentrations were 20.9 ± 11.5 ng/mL at baseline , with 57 % having 25(OH)D concentrations less than 20 ng/mL. Retention and adherence were high ( > 90 % ) . After the 5-month intervention , only one of 34 participants r and omized to vitamin D3 had 25(OH)D concentrations less than 20 ng/mL , compared with 18 of 25 participants r and omized to placebo ( P < .001 ) . In unadjusted analyses , the rate of falls over 5 months was not significantly different according to intervention group ( risk ratio ( RR ) = 0.48 , 95 % confidence interval ( CI ) = 0.19 - 1.19 ) , but after adjustment for sex , race , season of year , baseline 25(OH)D status , and history of falls , participants r and omized to vitamin D3 had a lower rate of falling than those r and omized to placebo ( RR = 0.42 , 95 % CI = 0.21 - 0.87 ) . CONCLUSION A vitamin D intervention delivered through MOW was feasible , result ing in improvements in 25(OH)D concentrations and a lower rate of falls in adjusted analyses . Further research is needed to vali date the reduction in falls from this type of intervention IMPORTANCE Observational studies suggest that vitamin D supplementation is associated with benefits for knee osteoarthritis , but current trial evidence is contradictory . OBJECTIVE To compare the effects of vitamin D supplementation vs placebo on knee pain and knee cartilage volume in patients with symptomatic knee osteoarthritis and low vitamin D levels . DESIGN , SETTING , AND PARTICIPANTS A multicenter r and omized , double-blind , placebo-controlled clinical trial in Tasmania and Victoria , Australia . Participants with symptomatic knee osteoarthritis and low 25-hydroxyvitamin D ( 12.5 - 60 nmol/L ) were enrolled from June 2010 to December 2011 . The trial was completed in December 2013 . INTERVENTIONS Participants were r and omly assigned to receive monthly treatment with oral vitamin D3 ( 50,000 IU ; n = 209 ) or an identical placebo ( n = 204 ) for 2 years . MAIN OUTCOMES AND MEASURES Primary outcomes were change in tibial cartilage volume ( assessed using magnetic resonance imaging [ MRI ] ) and change in the Western Ontario and McMaster Universities Arthritis Index ( WOMAC ) pain score ( 0 [ no pain ] to 500 [ worst pain ] ) from baseline to month 24 . Secondary outcomes were cartilage defects and bone marrow lesions ( assessed using MRI ) . RESULTS Of 413 enrolled participants ( mean age , 63.2 years ; 50 % women ) , 340 ( 82.3 % ) completed the study . The level of 25-hydroxyvitamin D increased more in the vitamin D group ( 40.6 nmol/L ) than in the placebo group ( 6.7 nmol/L ) ( P < .001 ) over 2 years . There were no significant differences in annual change of tibial cartilage volume or WOMAC pain score . There were no significant differences in change of tibiofemoral cartilage defects or change in tibiofemoral bone marrow lesions . Adverse events ( ≥ 1 per patient ) occurred in 56 participants in the vitamin D group and in 37 participants in the placebo group ( P = .04 ) . [ table : see text ] . CONCLUSIONS AND RELEVANCE Among patients with symptomatic knee osteoarthritis and low serum 25-hydroxyvitamin D levels  , vitamin D supplementation , compared with placebo , did not result in significant differences in change in MRI-measured tibial cartilage volume or WOMAC knee pain score over 2 years . These findings do not support the use of vitamin D supplementation for preventing tibial cartilage loss or improving WOMAC knee pain in patients with knee osteoarthritis . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01176344 ; anzctr.org.au Identifier : ACTRN12610000495022 IMPORTANCE Vitamin D deficiency has been associated with poor physical performance . OBJECTIVE To determine the effectiveness of high-dose vitamin D in lowering the risk of functional decline . DESIGN , SETTING , AND PARTICIPANTS One-year , double-blind , r and omized clinical trial conducted in Zurich , Switzerl and . The screening phase was December 1 , 2009 , to May 31 , 2010 , and the last study visit was in May 2011 . The date s of our analysis were June 15 , 2012 , to October 10 , 2015 . Participants were 200 community-dwelling men and women 70 years and older with a prior fall . INTERVENTIONS Three study groups with monthly treatments , including a low-dose control group receiving 24,000 IU of vitamin D3 ( 24,000 IU group ) , a group receiving 60,000 IU of vitamin D3 ( 60,000 IU group ) , and a group receiving 24,000 IU of vitamin D3 plus 300 μg of calcifediol ( 24,000 IU plus calcifediol group ) . MAIN OUTCOMES AND MEASURES The primary end point was improving lower extremity function ( on the Short Physical Performance Battery ) and achieving 25-hydroxyvitamin D levels of at least 30 ng/mL at 6 and 12 months . A secondary end point was monthly reported falls . Analyses were adjusted for age , sex , and body mass index . RESULTS The study cohort comprised 200 participants ( men and women ≥ 70 years with a prior fall ) . Their mean age was 78 years , 67.0 % ( 134 of 200 ) were female , and 58.0 % ( 116 of 200 ) were vitamin D deficient ( < 20 ng/mL ) at baseline . Intent-to-treat analyses showed that , while 60,000 IU and 24,000 IU plus calcifediol were more likely than 24,000 IU to result in 25-hydroxyvitamin D levels of at least 30 ng/mL ( P = .001 ) , they were not more effective in improving lower extremity function , which did not differ among the treatment groups ( P = .26 ) . However , over the 12-month follow-up , the incidence of falls differed significantly among the treatment groups , with higher incidences in the 60,000 IU group ( 66.9 % ; 95 % CI , 54.4 % to 77.5 % ) and the 24,000 IU plus calcifediol group ( 66.1 % ; 95 % CI , 53.5%-76.8 % ) group compared with the 24,000 IU group ( 47.9 % ; 95 % CI , 35.8%-60.3 % ) ( P = .048 ) . Consistent with the incidence of falls , the mean number of falls differed marginally by treatment group . The 60,000 IU group ( mean , 1.47 ) and the 24,000 IU plus calcifediol group ( mean , 1.24 ) had higher mean numbers of falls compared with the 24,000 IU group ( mean , 0.94 ) ( P = .09 ) . CONCLUSIONS AND RELEVANCE Although higher monthly doses of vitamin D were effective in reaching a threshold of at least 30 ng/mL of 25-hydroxyvitamin D , they had no benefit on lower extremity function and were associated with increased risk of falls compared with 24,000 IU . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01017354 Background : Low bone mineral density ( BMD ) is a significant comorbidity in HIV . However , studies evaluating vitamin D supplementation on bone health in this population are limited . This study investigates changes in bone health parameters after 12 months of supplementation in HIV-infected youth with vitamin D insufficiency . Methods : This is a r and omized , active-control , double-blind trial investigating changes in bone parameters with 3 different 
    Output:
    
agent
For hip fracture , at a 15 % relative risk , the effect estimate lay between the futility boundary and the inferior boundary , meaning there is reliable evidence that vitamin D supplementation does not reduce hip fractures by this amount , but uncertainty remains as to whether it might increase hip fractures .
The effect estimate lay within the futility boundary at thresholds of 0·5 % for total hip , forearm , and total body bone mineral density , and 1·0 % for lumbar spine and femoral neck , providing reliable evidence that vitamin D does not alter these outcomes by these amounts .
INTERPRETATION Our findings suggest that vitamin D supplementation does not prevent fractures or falls , or have clinical ly meaningful effects on bone mineral density .
There were no differences between the effects of higher and lower doses of vitamin D. There is little justification to use vitamin D supplements to maintain or improve musculoskeletal health .
***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 —Low 25-hydroxyvitamin D levels , commonly found in older patients with heart failure , may contribute to the chronic inflammation and skeletal myopathy that lead to poor exercise tolerance . We tested whether vitamin D supplementation of patients with heart failure and vitamin D insufficiency can improve physical function and quality of life . Methods and Results —In a r and omized , parallel group , double-blind , placebo-controlled trial , patients with systolic heart failure aged ≥70 years with 25-hydroxyvitamin D levels < 50 nmol/L ( 20 ng/mL ) received 100000 U of oral vitamin D2 or placebo at baseline and 10 weeks . Outcomes measured at baseline , 10 weeks , and 20 weeks were 6-minute walk distance , quality of life ( Minnesota score ) , daily activity measured by accelerometry , Functional Limitations Profile , B-type natriuretic peptide , and tumor necrosis factor-&agr;. Participants in the vitamin D group had an increase in their 25-hydroxyvitamin D levels compared with placebo at 10 weeks ( 22.9 versus 2.3 nmol/L [ 9.2 versus 0.9 ng/mL ] ; P<0.001 ) and maintained this increase at 20 weeks . The 6-minute walk did not improve in the treatment group relative to placebo . No significant benefit was seen on timed up and go testing , subjective measures of function , daily activity , or tumor necrosis factor . Quality of life worsened by a small , but significant amount in the treatment group relative to placebo . B-type natriuretic peptide decreased in the treatment group relative to placebo ( −22 versus + 78 pg/mL at 10 weeks ; P=0.04 ) . Conclusions —Vitamin D supplementation did not improve functional capacity or quality of life in older patients with heart failure with vitamin D insufficiency . Clinical Trial Registration —www.controlled-trials.com . Identifier : IS RCT N51372896 Background In meta-analyses supplementation with vitamin D appears to reduce incidence of fractures , and in cross-sectional studies there is a positive association between serum 25-hydroxyvitamin D ( 25(OH)D ) levels and bone mineral density ( BMD ) . However , the effect of supplementation with high doses of vitamin D on BMD is more uncertain and could in theory have both positive and negative effects . Methods The study was a one year , double blind placebo-controlled intervention trial performed at the University Hospital of North Norway . 421 subjects , 21 - 70 years old , were included and 312 completed the study . The subjects were r and omized to vitamin D3 40.000 IU per week ( DD group ) , vitamin D3 20.000 IU per week ( DP group ) , or placebo ( PP group ) . All subjects were given 500 mg calcium daily . Serum 25(OH)D , osteoprotegrin ( OPG ) , receptoractivator of nuclear factor-kappaB lig and ( RANKL ) , and BMD at the lumbar spine and the hip were measured before and at the end of the study . Results At baseline the mean serum 25(OH)D levels were 58 nmol/L ( all subjects ) and increased to 141 and 100 nmol/L in the DD and DP groups , respectively . After one year , no significant differences were found between the three groups regarding change in BMD , serum OPG or RANKL . Conclusions Supplementation with high doses of vitamin D for one year does not appear to have a negative effect on  BMD in healthy subjects . In order to disclose a positive effect , subjects with low BMD and /or low serum 25(OH)D levels need to be studied . Trial registration The trial was registered at Clinical Trials.gov ( NCT00243256 ) OBJECTIVES To assess the feasibility of a vitamin D intervention delivered through a Meals-on-Wheels ( MOW ) program to improve 25-hydroxyvitamin D ( 25(OH)D ) concentrations and reduce falls in homebound older adults . DESIGN Single-blind , cluster r and omized trial . SETTING MOW , Forsyth County , North Carolina . PARTICIPANTS Community-dwelling homebound adults aged 65 to 102 ( N = 68 ) . INTERVENTION MOW clients were r and omized to vitamin D3 ( 100,000 IU/month ; n = 38 ) or active placebo ( 400 IU vitamin E/month ; n = 30 ) according to MOW delivery route . MEASUREMENTS Serum 25(OH)D was assessed at baseline and 5-month follow-up ; proportions of participants in 25(OH)D categories were compared using Fisher exact test . Falls were assessed using monthly fall calendars , and rate of falls was estimated using negative binomial generalized estimating equation models . RESULTS Mean ± st and ard deviation 25(OH)D concentrations were 20.9 ± 11.5 ng/mL at baseline , with 57 % having 25(OH)D concentrations less than 20 ng/mL. Retention and adherence were high ( > 90 % ) . After the 5-month intervention , only one of 34 participants r and omized to vitamin D3 had 25(OH)D concentrations less than 20 ng/mL , compared with 18 of 25 participants r and omized to placebo ( P < .001 ) . In unadjusted analyses , the rate of falls over 5 months was not significantly different according to intervention group ( risk ratio ( RR ) = 0.48 , 95 % confidence interval ( CI ) = 0.19 - 1.19 ) , but after adjustment for sex , race , season of year , baseline 25(OH)D status , and history of falls , participants r and omized to vitamin D3 had a lower rate of falling than those r and omized to placebo ( RR = 0.42 , 95 % CI = 0.21 - 0.87 ) . CONCLUSION A vitamin D intervention delivered through MOW was feasible , result ing in improvements in 25(OH)D concentrations and a lower rate of falls in adjusted analyses . Further research is needed to vali date the reduction in falls from this type of intervention IMPORTANCE Observational studies suggest that vitamin D supplementation is associated with benefits for knee osteoarthritis , but current trial evidence is contradictory . OBJECTIVE To compare the effects of vitamin D supplementation vs placebo on knee pain and knee cartilage volume in patients with symptomatic knee osteoarthritis and low vitamin D levels . DESIGN , SETTING , AND PARTICIPANTS A multicenter r and omized , double-blind , placebo-controlled clinical trial in Tasmania and Victoria , Australia . Participants with symptomatic knee osteoarthritis and low 25-hydroxyvitamin D ( 12.5 - 60 nmol/L ) were enrolled from June 2010 to December 2011 . The trial was completed in December 2013 . INTERVENTIONS Participants were r and omly assigned to receive monthly treatment with oral vitamin D3 ( 50,000 IU ; n = 209 ) or an identical placebo ( n = 204 ) for 2 years . MAIN OUTCOMES AND MEASURES Primary outcomes were change in tibial cartilage volume ( assessed using magnetic resonance imaging [ MRI ] ) and change in the Western Ontario and McMaster Universities Arthritis Index ( WOMAC ) pain score ( 0 [ no pain ] to 500 [ worst pain ] ) from baseline to month 24 . Secondary outcomes were cartilage defects and bone marrow lesions ( assessed using MRI ) . RESULTS Of 413 enrolled participants ( mean age , 63.2 years ; 50 % women ) , 340 ( 82.3 % ) completed the study . The level of 25-hydroxyvitamin D increased more in the vitamin D group ( 40.6 nmol/L ) than in the placebo group ( 6.7 nmol/L ) ( P < .001 ) over 2 years . There were no significant differences in annual change of tibial cartilage volume or WOMAC pain score . There were no significant differences in change of tibiofemoral cartilage defects or change in tibiofemoral bone marrow lesions . Adverse events ( ≥ 1 per patient ) occurred in 56 participants in the vitamin D group and in 37 participants in the placebo group ( P = .04 ) . [ table : see text ] . CONCLUSIONS AND RELEVANCE Among patients with symptomatic knee osteoarthritis and low serum 25-hydroxyvitamin D levels  , vitamin D supplementation , compared with placebo , did not result in significant differences in change in MRI-measured tibial cartilage volume or WOMAC knee pain score over 2 years . These findings do not support the use of vitamin D supplementation for preventing tibial cartilage loss or improving WOMAC knee pain in patients with knee osteoarthritis . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01176344 ; anzctr.org.au Identifier : ACTRN12610000495022 IMPORTANCE Vitamin D deficiency has been associated with poor physical performance . OBJECTIVE To determine the effectiveness of high-dose vitamin D in lowering the risk of functional decline . DESIGN , SETTING , AND PARTICIPANTS One-year , double-blind , r and omized clinical trial conducted in Zurich , Switzerl and . The screening phase was December 1 , 2009 , to May 31 , 2010 , and the last study visit was in May 2011 . The date s of our analysis were June 15 , 2012 , to October 10 , 2015 . Participants were 200 community-dwelling men and women 70 years and older with a prior fall . INTERVENTIONS Three study groups with monthly treatments , including a low-dose control group receiving 24,000 IU of vitamin D3 ( 24,000 IU group ) , a group receiving 60,000 IU of vitamin D3 ( 60,000 IU group ) , and a group receiving 24,000 IU of vitamin D3 plus 300 μg of calcifediol ( 24,000 IU plus calcifediol group ) . MAIN OUTCOMES AND MEASURES The primary end point was improving lower extremity function ( on the Short Physical Performance Battery ) and achieving 25-hydroxyvitamin D levels of at least 30 ng/mL at 6 and 12 months . A secondary end point was monthly reported falls . Analyses were adjusted for age , sex , and body mass index . RESULTS The study cohort comprised 200 participants ( men and women ≥ 70 years with a prior fall ) . Their mean age was 78 years , 67.0 % ( 134 of 200 ) were female , and 58.0 % ( 116 of 200 ) were vitamin D deficient ( < 20 ng/mL ) at baseline . Intent-to-treat analyses showed that , while 60,000 IU and 24,000 IU plus calcifediol were more likely than 24,000 IU to result in 25-hydroxyvitamin D levels of at least 30 ng/mL ( P = .001 ) , they were not more effective in improving lower extremity function , which did not differ among the treatment groups ( P = .26 ) . However , over the 12-month follow-up , the incidence of falls differed significantly among the treatment groups , with higher incidences in the 60,000 IU group ( 66.9 % ; 95 % CI , 54.4 % to 77.5 % ) and the 24,000 IU plus calcifediol group ( 66.1 % ; 95 % CI , 53.5%-76.8 % ) group compared with the 24,000 IU group ( 47.9 % ; 95 % CI , 35.8%-60.3 % ) ( P = .048 ) . Consistent with the incidence of falls , the mean number of falls differed marginally by treatment group . The 60,000 IU group ( mean , 1.47 ) and the 24,000 IU plus calcifediol group ( mean , 1.24 ) had higher mean numbers of falls compared with the 24,000 IU group ( mean , 0.94 ) ( P = .09 ) . CONCLUSIONS AND RELEVANCE Although higher monthly doses of vitamin D were effective in reaching a threshold of at least 30 ng/mL of 25-hydroxyvitamin D , they had no benefit on lower extremity function and were associated with increased risk of falls compared with 24,000 IU . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01017354 Background : Low bone mineral density ( BMD ) is a significant comorbidity in HIV . However , studies evaluating vitamin D supplementation on bone health in this population are limited . This study investigates changes in bone health parameters after 12 months of supplementation in HIV-infected youth with vitamin D insufficiency . Methods : This is a r and omized , active-control , double-blind trial investigating changes in bone parameters with 3 different 
    Output:
    