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: OBJECTIVES A high prevalence of hip and other fractures in elderly patients with Parkinson ’s disease has been linked to reduced bone mass arising from a defect of renal synthesis of 1 , 25-dihydroxyvitamin D ( 1 , 25-[OH]2D ) . Treatment with 1α-hydroxyvitamin D3 ( 1α(OH)D3 ; an active form of vitamin D ) was evaluated for maintaining bone mass and reducing the incidence of hip and other non-vertebral fractures in patients with Parkinson ’s disease . METHODS In a double blind , r and omised trial , 86 elderly patients with Parkinson ’s disease ( mean Hoehn and Yahr stage , 3 ; mean age 70.6 years ) were r and omised to receive either 1 μg 1α(OH)D3 daily ( treatment group , n=43 ) or a placebo ( n=43 ) for 18 months . Bone mineral densities in the second metacarpals were determined by computed radiographic densitometry . Serum bone turnover indices were measured serially , and incidence of non-vertebral fractures was recorded . RESULTS Bone mineral densities decreased 1.2 % in the treatment group compared with 6.7 % in the placebo group during 18 months ( p<0.0001 ) . At baseline in both groups , the serum concentration of 1 , 25-[OH]2D was reduced . Parathyroid hormone was abnormally increased in 15 patients ( 17 % ) and correlated negatively with serum 25-hydroxyvitamin D , indicating compensatory hyperparathyroidism . Eight patients  sustained fractures ( six at the hip and two at other sites ) in the placebo group , and one hip fracture occurred among treated patients ( odds ratio 9.8 ; p=0.0028 ) . CONCLUSION By increasing serum 1 , 25-[OH]2D concentrations , treatment with 1α(OH)D3 can reduce the risk of hip and other non-vertebral fractures in osteoporotic elderly patients with Parkinson ’s disease by slowing the loss of bone mineral densities BACKGROUND Low serum 25-hydroxyvitamin D ( 25-[OH]D ) levels have been associated with lower FEV(1 ) , impaired immunologic control , and increased airway inflammation . Because many patients with chronic obstructive pulmonary disease ( COPD ) have vitamin D deficiency , effects of vitamin D supplementation may extend beyond preventing osteoporosis . OBJECTIVE To explore whether supplementation with high doses of vitamin D could reduce the incidence of COPD exacerbations . DESIGN R and omized , single-center , double-blind , placebo-controlled trial . ( Clinical Trials.gov registration number : NCT00666367 ) SETTING University Hospitals Leuven , Leuven , Belgium . PATIENTS 182 patients with moderate to very severe COPD and a history of recent exacerbations . INTERVENTION 100,000 IU of vitamin D supplementation or placebo every 4 weeks for 1 year . MEASUREMENTS The primary outcome was time to first exacerbation . Secondary outcomes were exacerbation rate , time to first hospitalization , time to second exacerbation , FEV(1 ) , quality of life , and death . RESULTS Mean serum 25-(OH)D levels increased significantly in the vitamin D group compared with the placebo group ( mean between-group difference , 30 ng/mL [ 95 % CI , 27 to 33 ng/mL ] ; P < 0.001 ) . The median time to first exacerbation did not significantly differ between the groups ( hazard ratio , 1.1 [ CI , 0.82 to 1.56 ] ; P = 0.41 ) , nor did exacerbation rates , FEV(1 ) , hospitalization , quality of life , and death . However , a post hoc analysis in 30 participants with severe vitamin D deficiency ( serum 25-[OH]D levels < 10 ng/mL ) at baseline showed a significant reduction in exacerbations in the vitamin D group ( rate ratio , 0.57 [ CI , 0.33 to 0.98 ] ; P = 0.042 ) . LIMITATION This was a single-center study with a small sample size . CONCLUSION High-dose vitamin D supplementation in a sample of patients with COPD did not reduce the incidence of exacerbations . In participants with severe vitamin D deficiency at baseline , supplementation may reduce exacerbations . PRIMARY FUNDING SOURCE Applied Biomedical Research Program , Agency for Innovation by Science and Technology ( IWT-TBM ) An unexplained loss of muscle strength occurs with aging . Vitamin D deficiency can cause myopathy and administration of 1,25-dihydroxyvitamin D3 [ 1,25-(OH2)D3 ] to persons with low serum concentrations can improve strength . To test the hypothesis that the weakness associated with aging is in part due to inadequate serum concentrations of [ 1,25-(OH2)D3 ] , we conducted a r and omized , controlled , double blinded trial in 98 men and women volunteers over 69 yr old . Treatment consisted of 0.25 micrograms 1,25-(OH)2D3 , orally , twice per day or identical placebo for 6 months .  Leg muscle strength of the quadriceps was measured with an isokinetic dynamometer . There was no difference between the two groups at 1 week , 1 month , or 6 months of treatment in any of the measures of muscle strength . We conclude that oral administration of 0.5 micrograms 1,25-(OH)2D3/day does not improve muscle strength in older persons . Further research is needed to determine the etiology of the decline in muscle strength associated with aging 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 Estrogen deficiency and declining calcium absorption due to reduced calcitriol levels or intestinal resistance to calcitriol , are important factors in the pathogenesis of age-related bone loss . The main objective of this study was to examine the effect of estrogen and 1,25-dihydroxyvitamin D therapy given individually or in combination on  bone loss in elderly women . Four hundred eighty-nine elderly women with normal bone density for their age , aged 65 - 77 yr , were entered into a r and omized double blind , placebo-controlled trial . Women were r and omized to one of four groups : conjugated estrogens ( 0.625 mg , daily ) to women without a uterus ( estrogen replacement therapy ) plus medroxyprogesterone acetate ( 2.5 mg , daily ) to women with a uterus ( hormone replacement therapy ) , calcitriol ( 0.25 microg twice daily ) , a combination of hormone replacement therapy/estrogen replacement therapy plus calcitriol , or placebos for 3 yr . The primary outcome was the change in bone mineral density of the femoral neck and spine . In the intent to treat analysis , hormone therapy ( hormone replacement therapy/estrogen replacement therapy ) produced a mean ( + /-1 SD ) increase in bone mineral density of 2.98 % ( + /-5.45 % ) at the femoral neck ( P < 0.0001 ) and 4.36 % ( + /-6.42 % ) at the spine ( P < 0.0001 ) . There were parallel increases in total hip and trochanter bone mineral density . Calcitriol increased bone mineral density 0.10 % ( + /- 4.27 % ) at the femoral neck ( P = 0.57 ) and 1.65 % ( + /- 4.83 % ) at the spine ( P < 0.0124 ) . The combination of hormone replacement therapy/estrogen replacement therapy + calcitriol  increased bone mineral density 3.80 % ( + /-4.95 % ) at the femoral neck ( P < 0.001 ) , 4.91 % ( + /-6.0 % ) at the spine ( P < 0.0001 ) , and parallel changes at the total hip and trochanter . All three treatment groups differed significantly from placebo at the spine and for the hormone replacement therapy/estrogen replacement therapy groups at the femoral neck , spine , total hip and trochanter . There were no significant differences between combination therapy and hormone replacement therapy/estrogen replacement therapy alone on bone mineral density at any site in the intent to treat analysis . In a secondary analysis of the effect in women who were adherent to treatment , calcitriol had a more significant effect on spine ( P = 0.003 ) and total hip ( P = 0.004 ) . The increase in bone mineral density in the adherent groups of women was always higher compared with the intent to treat groups . Combination therapy compared with hormone replacement therapy/estrogen replacement therapy alone produced a significantly greater response in trochanter ( P = 0.007 ) and total hip bone mineral density ( P = 0.0017 ) . In summary , hormone replacement therapy/estrogen replacement therapy alone and in combination with calcitriol therapy was highly effective in reducing bone resorption and increasing bone mineral density at the hip and other clinical ly relevant sites in a group of elderly women , with normal bone density for their age . Calcitriol was effective in increasing spine bone mineral density . In the adherent women , combination therapy with hormone replacement therapy/estrogen replacement therapy and calcitriol increased bone mineral density significantly more in the total hip and trochanter than did hormone replacement therapy/estrogen replacement therapy alone 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 
    Output:
    
agent
In subgroup analyses , all cause mortality was significantly lower in trials with vitamin D3 supplementation than in trials with vitamin D2 supplementation ( P for interaction=0.04 ) ; neither vitamin D3 nor vitamin D2 was associated with a statistically significant reduction in all cause mortality .
CONCLUSIONS Vitamin D supplementation alone was not associated with  all cause mortality in adults compared with placebo or no treatment .
Vitamin D supplementation reduced the risk of cancer death by 16 % .
Additional large clinical studies are needed to determine whether vitamin D3 supplementation is associated with lower all cause mortality .
***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: OBJECTIVES A high prevalence of hip and other fractures in elderly patients with Parkinson ’s disease has been linked to reduced bone mass arising from a defect of renal synthesis of 1 , 25-dihydroxyvitamin D ( 1 , 25-[OH]2D ) . Treatment with 1α-hydroxyvitamin D3 ( 1α(OH)D3 ; an active form of vitamin D ) was evaluated for maintaining bone mass and reducing the incidence of hip and other non-vertebral fractures in patients with Parkinson ’s disease . METHODS In a double blind , r and omised trial , 86 elderly patients with Parkinson ’s disease ( mean Hoehn and Yahr stage , 3 ; mean age 70.6 years ) were r and omised to receive either 1 μg 1α(OH)D3 daily ( treatment group , n=43 ) or a placebo ( n=43 ) for 18 months . Bone mineral densities in the second metacarpals were determined by computed radiographic densitometry . Serum bone turnover indices were measured serially , and incidence of non-vertebral fractures was recorded . RESULTS Bone mineral densities decreased 1.2 % in the treatment group compared with 6.7 % in the placebo group during 18 months ( p<0.0001 ) . At baseline in both groups , the serum concentration of 1 , 25-[OH]2D was reduced . Parathyroid hormone was abnormally increased in 15 patients ( 17 % ) and correlated negatively with serum 25-hydroxyvitamin D , indicating compensatory hyperparathyroidism . Eight patients  sustained fractures ( six at the hip and two at other sites ) in the placebo group , and one hip fracture occurred among treated patients ( odds ratio 9.8 ; p=0.0028 ) . CONCLUSION By increasing serum 1 , 25-[OH]2D concentrations , treatment with 1α(OH)D3 can reduce the risk of hip and other non-vertebral fractures in osteoporotic elderly patients with Parkinson ’s disease by slowing the loss of bone mineral densities BACKGROUND Low serum 25-hydroxyvitamin D ( 25-[OH]D ) levels have been associated with lower FEV(1 ) , impaired immunologic control , and increased airway inflammation . Because many patients with chronic obstructive pulmonary disease ( COPD ) have vitamin D deficiency , effects of vitamin D supplementation may extend beyond preventing osteoporosis . OBJECTIVE To explore whether supplementation with high doses of vitamin D could reduce the incidence of COPD exacerbations . DESIGN R and omized , single-center , double-blind , placebo-controlled trial . ( Clinical Trials.gov registration number : NCT00666367 ) SETTING University Hospitals Leuven , Leuven , Belgium . PATIENTS 182 patients with moderate to very severe COPD and a history of recent exacerbations . INTERVENTION 100,000 IU of vitamin D supplementation or placebo every 4 weeks for 1 year . MEASUREMENTS The primary outcome was time to first exacerbation . Secondary outcomes were exacerbation rate , time to first hospitalization , time to second exacerbation , FEV(1 ) , quality of life , and death . RESULTS Mean serum 25-(OH)D levels increased significantly in the vitamin D group compared with the placebo group ( mean between-group difference , 30 ng/mL [ 95 % CI , 27 to 33 ng/mL ] ; P < 0.001 ) . The median time to first exacerbation did not significantly differ between the groups ( hazard ratio , 1.1 [ CI , 0.82 to 1.56 ] ; P = 0.41 ) , nor did exacerbation rates , FEV(1 ) , hospitalization , quality of life , and death . However , a post hoc analysis in 30 participants with severe vitamin D deficiency ( serum 25-[OH]D levels < 10 ng/mL ) at baseline showed a significant reduction in exacerbations in the vitamin D group ( rate ratio , 0.57 [ CI , 0.33 to 0.98 ] ; P = 0.042 ) . LIMITATION This was a single-center study with a small sample size . CONCLUSION High-dose vitamin D supplementation in a sample of patients with COPD did not reduce the incidence of exacerbations . In participants with severe vitamin D deficiency at baseline , supplementation may reduce exacerbations . PRIMARY FUNDING SOURCE Applied Biomedical Research Program , Agency for Innovation by Science and Technology ( IWT-TBM ) An unexplained loss of muscle strength occurs with aging . Vitamin D deficiency can cause myopathy and administration of 1,25-dihydroxyvitamin D3 [ 1,25-(OH2)D3 ] to persons with low serum concentrations can improve strength . To test the hypothesis that the weakness associated with aging is in part due to inadequate serum concentrations of [ 1,25-(OH2)D3 ] , we conducted a r and omized , controlled , double blinded trial in 98 men and women volunteers over 69 yr old . Treatment consisted of 0.25 micrograms 1,25-(OH)2D3 , orally , twice per day or identical placebo for 6 months .  Leg muscle strength of the quadriceps was measured with an isokinetic dynamometer . There was no difference between the two groups at 1 week , 1 month , or 6 months of treatment in any of the measures of muscle strength . We conclude that oral administration of 0.5 micrograms 1,25-(OH)2D3/day does not improve muscle strength in older persons . Further research is needed to determine the etiology of the decline in muscle strength associated with aging 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 Estrogen deficiency and declining calcium absorption due to reduced calcitriol levels or intestinal resistance to calcitriol , are important factors in the pathogenesis of age-related bone loss . The main objective of this study was to examine the effect of estrogen and 1,25-dihydroxyvitamin D therapy given individually or in combination on  bone loss in elderly women . Four hundred eighty-nine elderly women with normal bone density for their age , aged 65 - 77 yr , were entered into a r and omized double blind , placebo-controlled trial . Women were r and omized to one of four groups : conjugated estrogens ( 0.625 mg , daily ) to women without a uterus ( estrogen replacement therapy ) plus medroxyprogesterone acetate ( 2.5 mg , daily ) to women with a uterus ( hormone replacement therapy ) , calcitriol ( 0.25 microg twice daily ) , a combination of hormone replacement therapy/estrogen replacement therapy plus calcitriol , or placebos for 3 yr . The primary outcome was the change in bone mineral density of the femoral neck and spine . In the intent to treat analysis , hormone therapy ( hormone replacement therapy/estrogen replacement therapy ) produced a mean ( + /-1 SD ) increase in bone mineral density of 2.98 % ( + /-5.45 % ) at the femoral neck ( P < 0.0001 ) and 4.36 % ( + /-6.42 % ) at the spine ( P < 0.0001 ) . There were parallel increases in total hip and trochanter bone mineral density . Calcitriol increased bone mineral density 0.10 % ( + /- 4.27 % ) at the femoral neck ( P = 0.57 ) and 1.65 % ( + /- 4.83 % ) at the spine ( P < 0.0124 ) . The combination of hormone replacement therapy/estrogen replacement therapy + calcitriol  increased bone mineral density 3.80 % ( + /-4.95 % ) at the femoral neck ( P < 0.001 ) , 4.91 % ( + /-6.0 % ) at the spine ( P < 0.0001 ) , and parallel changes at the total hip and trochanter . All three treatment groups differed significantly from placebo at the spine and for the hormone replacement therapy/estrogen replacement therapy groups at the femoral neck , spine , total hip and trochanter . There were no significant differences between combination therapy and hormone replacement therapy/estrogen replacement therapy alone on bone mineral density at any site in the intent to treat analysis . In a secondary analysis of the effect in women who were adherent to treatment , calcitriol had a more significant effect on spine ( P = 0.003 ) and total hip ( P = 0.004 ) . The increase in bone mineral density in the adherent groups of women was always higher compared with the intent to treat groups . Combination therapy compared with hormone replacement therapy/estrogen replacement therapy alone produced a significantly greater response in trochanter ( P = 0.007 ) and total hip bone mineral density ( P = 0.0017 ) . In summary , hormone replacement therapy/estrogen replacement therapy alone and in combination with calcitriol therapy was highly effective in reducing bone resorption and increasing bone mineral density at the hip and other clinical ly relevant sites in a group of elderly women , with normal bone density for their age . Calcitriol was effective in increasing spine bone mineral density . In the adherent women , combination therapy with hormone replacement therapy/estrogen replacement therapy and calcitriol increased bone mineral density significantly more in the total hip and trochanter than did hormone replacement therapy/estrogen replacement therapy alone 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 
    Output:
    