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: 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 The Cohort Consortium Vitamin D Pooling Project of Rarer Cancers ( VDPP ) brought together 10 cohorts to conduct a prospect i ve study of the association between vitamin D status , measured as serum concentrations of 25-hydroxyvitamin D ( 25(OH)D ) , and the development of 7 rarer cancer sites : endometrial , esophageal , gastric , kidney , non-Hodgkin lymphoma , ovarian , and pancreatic cancers . The cohorts come from 3 continents , with participants from a wide range of latitude who are racially diverse . Across each cancer site , there was no evidence of a protective association between higher concentrations of 25-hydroxyvitamin D ( > 75 nmol/L ) and cancer outcome . An increased risk at very high levels ( ≥100 nmol/L ) was noted for pancreatic cancer , confirming previous reports . The articles included in this issue detail the overall design and governance of the project , correlates of vitamin D status , and results from the cancer site-specific investigations . The Vitamin D Pooling Project realizes a major goal of consortium efforts , namely , to rigorously test hypotheses for rarer cancer outcomes that may not be adequately addressed in any one prospect i ve cohort study . The results of this study have application for the planning and conduct of intervention trials , especially in determining potential risks 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 CONTEXT Observational studies show an association between low vitamin D status assessed by circulating 25-hydroxyvitamin D and cardiovascular events and mortality . Data from r and omized controlled trials are limited . OBJECTIVE The aim of this study was to test whether daily doses of vitamin D(3 ) at 400 or 1000 IU/d for 1 yr affected conventional markers of cardiovascular disease ( CVD ) risk . DESIGN We conducted a parallel-group , double-blind , placebo-controlled r and omized controlled trial . R and omization was computer generated . Participants and study investigators were blinded to intervention groupings throughout the trial . SETTING The study was conducted at the Clinical Research Facility , University of Aberdeen , United Kingdom . PARTICIPANTS A total of 305 healthy postmenopausal women aged 60 - 70 yr were recruited for the study . INTERVENTION Each woman received a daily capsule of 400 or 1000 IU vitamin D(3 ) or placebo r and omly allocated . MAIN OUTCOME MEASURES Primary outcomes were serum lipid profile [ total , high-density lipoprotein , and low-density lipoprotein cholesterol ; triglycerides ; and apolipoproteins A-1 and B100 ] , insulin resistance ( homeostatic model assessment ) , inflammatory biomarkers ( high-sensitivity C-reactive protein , IL-6 , soluble intracellular adhesion molecule-1 ) , and blood pressure . RESULTS A total of 265 ( 87 % ) participants completed all study visits . Small differences between groups for serum apolipoprotein B100 change [ repeated measures ANOVA , P=0.04 ; mean ( sd ) , -1.0 ( 10.0 ) mg/dl ( 400 IU ) ; -1.0 ( 10.0 ) mg/dl ( 1000 IU ) ; and + 0.02 ( 10.0 ) mg/dl ( placebo ) ] were not considered clinical ly significant . Other systemic markers for CVD risk remained unchanged . There was significant seasonal variation in systolic and diastolic blood pressure independent of vitamin D dose ( P<0.001 , linear mixed model ) . Mean ( sd ) reduction in systolic blood pressure from winter to summer was -6.6 ( 10.8 ) mm Hg . CONCLUSIONS Improving vitamin D status through dietary supplementation is unlikely to reduce CVD risk factors . Confounding of seasonality should be recognized and addressed in future studies of vitamin BACKGROUND There is a paucity of research evaluating the relation between  vitamin D  and recurrence of breast cancer after treatment . OBJECTIVE This study was design ed to evaluate the associations between circulating concentrations of  25-hydroxyvitamin D [ 25(OH)D ]  and dietary , supplemental , and total intake of vitamin D  and recurrent or new breast cancer events within the Women 's Healthy Eating and Living ( WHEL ) Study . DESIGN A prospect i ve cohort study design ( n = 3085 ) was used to evaluate the relation between dietary , supplemental , and total vitamin D intake and recurrent breast cancer , and a nested case-control study with 512 matched pairs was used for analysis of the association between 25(OH)D and breast cancer recurrence . RESULTS No relation between 25(OH)D and breast cancer recurrence was observed . Compared with women with serum concentrations of 25(OH)D ≥ 30 ng/mL , adjusted odds ratios ( 95 % CI ) for breast cancer recurrence were 1.14 ( 0.57 , 2.31 ) for those with concentrations < 10 ng/mL , 1.00 ( 0.68 - 1.48 ) for concentrations ≥ 10 and < 20 ng/mL , and 1.05 ( 0.76 , 1.47 ) for concentrations ≥ 20 and < 30 ng/mL. No significant associations were observed when analyses were stratified by pre- and postmenopausal status or for local , regional , or distant recurrence or death . Vitamin D intake was not related to breast cancer recurrence overall , although for premenopausal women there was a significant inverse association between dietary vitamin D intake and recurrence ( P for trend = 0.02 ) . CONCLUSION These results do not provide support for a relation between concentrations of 25(OH)D after treatment and the recurrence of breast cancer . This trial is registered at clinical trials.gov for the WHEL Study as NCT00003787 To evaluate the effects of alfacalcidol on bone turnover in elderly women with osteoporosis , an open-label , prospect i ve , calcium-controlled study was conducted . A total of 80 patients with osteoporosis were divided into two groups : the control group , group C ( mean age , 78.0 years ) , in which patients were given calcium , and group D ( mean age , 77.4 years ) , in which the patients were given alfacalcidol 1 µg/day together with calcium for 6 months . Calcium regulation , lumbar bone mineral density ( LBMD ) , and markers for bone turnover were assessed . A significant increase in urinary calcium/creatinine ratio ( 90 % increase from baseline at 3 months ; P = 0.0083 , and 60 % at 6 months ; P = 0.0091 ) and a significant decrease in serum parathyroid hormone ( 30 % decrease from baseline at 6 months ; P < 0.0001 ) was observed in group D compared with the corresponding changes in group C. Significant decreases of bone resorption markers ( deoxypyridinoline and N-telopeptide ) at 6 months ( about 15 % decrease from the baseline values ) were observed in group D compared with the corresponding changes in group C. The changes in bone formation markers ( bone-derived alkaline phosphatase and osteocalcin ) in group D were significantly different at 6 months ( −21.5 % ; P = 0.0047 and −13.4 % ; P = 0.0032 , respectively ) from the values in group C. The magnitudes of the decrease in bone turnover markers were highly correlated with the corresponding baseline values , suggesting that alfacalcidol treatment effectively reduces bone turnover in patients with high bone turnover rates . The LBMD in group D increased by 1.7 % and that in group C decreased by 1.6 % ( P = 0.0384 ) . The changes in calcium metabolism and LBMD were in good agreement with those in previous reports . Although the changes in bone turnover markers in group D were slight , significant reduction in bone turnover with alfacalcidol treatment , together with the change in calcium metabolism , may account for the effects of alfacalcidol on BMD and on fracture prevention reported previously . In conclusion , alfacalcidol reduces bone turnover  in elderly women with high-bone-turnover osteoporosis , and it may have beneficial effects on bone Experimental and epidemiological studies suggest that calcium and vitamin D supplements may lower  blood pressure . We examined the effect of calcium plus vitamin D supplementation on blood pressure and the incidence of hypertension in postmenopausal women . The Women 's Health Initiative Calcium/Vitamin D Trial r and omly assigned 36 282 postmenopausal women to receive 1000 mg of 
    Output:
    
agent
There is currently no firm evidence that vitamin D supplementation decreases or increases cancer occurrence in predominantly elderly community-dwelling women .
Vitamin D₃ supplementation  decreased cancer mortality  and vitamin D supplementation  decreased all-cause mortality , but these estimates are at risk of type I errors due to the fact that too few participants were examined , and to risks of attrition bias originating from substantial dropout of participants .
Combined vitamin D₃ and calcium supplements  increased nephrolithiasis , whereas it remains unclear from the included trials whether vitamin D₃ , calcium , or both were responsible for this effect .
***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: 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 The Cohort Consortium Vitamin D Pooling Project of Rarer Cancers ( VDPP ) brought together 10 cohorts to conduct a prospect i ve study of the association between vitamin D status , measured as serum concentrations of 25-hydroxyvitamin D ( 25(OH)D ) , and the development of 7 rarer cancer sites : endometrial , esophageal , gastric , kidney , non-Hodgkin lymphoma , ovarian , and pancreatic cancers . The cohorts come from 3 continents , with participants from a wide range of latitude who are racially diverse . Across each cancer site , there was no evidence of a protective association between higher concentrations of 25-hydroxyvitamin D ( > 75 nmol/L ) and cancer outcome . An increased risk at very high levels ( ≥100 nmol/L ) was noted for pancreatic cancer , confirming previous reports . The articles included in this issue detail the overall design and governance of the project , correlates of vitamin D status , and results from the cancer site-specific investigations . The Vitamin D Pooling Project realizes a major goal of consortium efforts , namely , to rigorously test hypotheses for rarer cancer outcomes that may not be adequately addressed in any one prospect i ve cohort study . The results of this study have application for the planning and conduct of intervention trials , especially in determining potential risks 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 CONTEXT Observational studies show an association between low vitamin D status assessed by circulating 25-hydroxyvitamin D and cardiovascular events and mortality . Data from r and omized controlled trials are limited . OBJECTIVE The aim of this study was to test whether daily doses of vitamin D(3 ) at 400 or 1000 IU/d for 1 yr affected conventional markers of cardiovascular disease ( CVD ) risk . DESIGN We conducted a parallel-group , double-blind , placebo-controlled r and omized controlled trial . R and omization was computer generated . Participants and study investigators were blinded to intervention groupings throughout the trial . SETTING The study was conducted at the Clinical Research Facility , University of Aberdeen , United Kingdom . PARTICIPANTS A total of 305 healthy postmenopausal women aged 60 - 70 yr were recruited for the study . INTERVENTION Each woman received a daily capsule of 400 or 1000 IU vitamin D(3 ) or placebo r and omly allocated . MAIN OUTCOME MEASURES Primary outcomes were serum lipid profile [ total , high-density lipoprotein , and low-density lipoprotein cholesterol ; triglycerides ; and apolipoproteins A-1 and B100 ] , insulin resistance ( homeostatic model assessment ) , inflammatory biomarkers ( high-sensitivity C-reactive protein , IL-6 , soluble intracellular adhesion molecule-1 ) , and blood pressure . RESULTS A total of 265 ( 87 % ) participants completed all study visits . Small differences between groups for serum apolipoprotein B100 change [ repeated measures ANOVA , P=0.04 ; mean ( sd ) , -1.0 ( 10.0 ) mg/dl ( 400 IU ) ; -1.0 ( 10.0 ) mg/dl ( 1000 IU ) ; and + 0.02 ( 10.0 ) mg/dl ( placebo ) ] were not considered clinical ly significant . Other systemic markers for CVD risk remained unchanged . There was significant seasonal variation in systolic and diastolic blood pressure independent of vitamin D dose ( P<0.001 , linear mixed model ) . Mean ( sd ) reduction in systolic blood pressure from winter to summer was -6.6 ( 10.8 ) mm Hg . CONCLUSIONS Improving vitamin D status through dietary supplementation is unlikely to reduce CVD risk factors . Confounding of seasonality should be recognized and addressed in future studies of vitamin BACKGROUND There is a paucity of research evaluating the relation between  vitamin D  and recurrence of breast cancer after treatment . OBJECTIVE This study was design ed to evaluate the associations between circulating concentrations of  25-hydroxyvitamin D [ 25(OH)D ]  and dietary , supplemental , and total intake of vitamin D  and recurrent or new breast cancer events within the Women 's Healthy Eating and Living ( WHEL ) Study . DESIGN A prospect i ve cohort study design ( n = 3085 ) was used to evaluate the relation between dietary , supplemental , and total vitamin D intake and recurrent breast cancer , and a nested case-control study with 512 matched pairs was used for analysis of the association between 25(OH)D and breast cancer recurrence . RESULTS No relation between 25(OH)D and breast cancer recurrence was observed . Compared with women with serum concentrations of 25(OH)D ≥ 30 ng/mL , adjusted odds ratios ( 95 % CI ) for breast cancer recurrence were 1.14 ( 0.57 , 2.31 ) for those with concentrations < 10 ng/mL , 1.00 ( 0.68 - 1.48 ) for concentrations ≥ 10 and < 20 ng/mL , and 1.05 ( 0.76 , 1.47 ) for concentrations ≥ 20 and < 30 ng/mL. No significant associations were observed when analyses were stratified by pre- and postmenopausal status or for local , regional , or distant recurrence or death . Vitamin D intake was not related to breast cancer recurrence overall , although for premenopausal women there was a significant inverse association between dietary vitamin D intake and recurrence ( P for trend = 0.02 ) . CONCLUSION These results do not provide support for a relation between concentrations of 25(OH)D after treatment and the recurrence of breast cancer . This trial is registered at clinical trials.gov for the WHEL Study as NCT00003787 To evaluate the effects of alfacalcidol on bone turnover in elderly women with osteoporosis , an open-label , prospect i ve , calcium-controlled study was conducted . A total of 80 patients with osteoporosis were divided into two groups : the control group , group C ( mean age , 78.0 years ) , in which patients were given calcium , and group D ( mean age , 77.4 years ) , in which the patients were given alfacalcidol 1 µg/day together with calcium for 6 months . Calcium regulation , lumbar bone mineral density ( LBMD ) , and markers for bone turnover were assessed . A significant increase in urinary calcium/creatinine ratio ( 90 % increase from baseline at 3 months ; P = 0.0083 , and 60 % at 6 months ; P = 0.0091 ) and a significant decrease in serum parathyroid hormone ( 30 % decrease from baseline at 6 months ; P < 0.0001 ) was observed in group D compared with the corresponding changes in group C. Significant decreases of bone resorption markers ( deoxypyridinoline and N-telopeptide ) at 6 months ( about 15 % decrease from the baseline values ) were observed in group D compared with the corresponding changes in group C. The changes in bone formation markers ( bone-derived alkaline phosphatase and osteocalcin ) in group D were significantly different at 6 months ( −21.5 % ; P = 0.0047 and −13.4 % ; P = 0.0032 , respectively ) from the values in group C. The magnitudes of the decrease in bone turnover markers were highly correlated with the corresponding baseline values , suggesting that alfacalcidol treatment effectively reduces bone turnover in patients with high bone turnover rates . The LBMD in group D increased by 1.7 % and that in group C decreased by 1.6 % ( P = 0.0384 ) . The changes in calcium metabolism and LBMD were in good agreement with those in previous reports . Although the changes in bone turnover markers in group D were slight , significant reduction in bone turnover with alfacalcidol treatment , together with the change in calcium metabolism , may account for the effects of alfacalcidol on BMD and on fracture prevention reported previously . In conclusion , alfacalcidol reduces bone turnover  in elderly women with high-bone-turnover osteoporosis , and it may have beneficial effects on bone Experimental and epidemiological studies suggest that calcium and vitamin D supplements may lower  blood pressure . We examined the effect of calcium plus vitamin D supplementation on blood pressure and the incidence of hypertension in postmenopausal women . The Women 's Health Initiative Calcium/Vitamin D Trial r and omly assigned 36 282 postmenopausal women to receive 1000 mg of 
    Output:
    