The Effect of Season and Vitamin D Supplementation on Bone Mineral Density in Healthy Women: A Double-Masked Crossover Study
 A randomized controlled trial of vitamin D3 supplementation in African American women. Vitamin D status in relation to obesity, bone mineral density, bone turnover markers and vitamin D receptor genotypes in healthy Saudi pre- and postmenopausal women Associations of vitamin D status with bone mineral density, bone turnover, bone loss and fracture risk in healthy postmenopausal women. The OFELY study. Effects of calcium and vitamin D supplementation on hip bone mineral density and calcium-related analytes in elderly ambulatory Australian women: a five-year randomized controlled trial. Cholecalciferol supplementation throughout winter does not affect markers of bone turnover in healthy young and elderly adults. Increased Bone Resorption in the Proximal Femur in Patients with Hemiplegia The Effect of High-Dose Vitamin D Supplementation on Calciotropic Hormones and Bone Mineral Density in Obese Subjects with Low Levels of Circulating 25-Hydroxyvitamin D: Results from a Randomized Controlled Study Randomised controlled trial of vitamin D supplementation in sarcoidosis Increased PTH and 1.25(OH)(2)D levels associated with increased markers of bone turnover following bariatric surgery. Skeletal Effects of Vitamin D Supplementation in Postmenopausal Black Women Vitamin D supplementation after parathyroidectomy: effect on bone mineral density-a randomized double-blind study. Vitamin D status and sex hormone binding globulin: determinants of bone turnover and bone mineral density in elderly women. Bone mineral density and bone markers in patients with a recent low-energy fracture: effect of 1 y of treatment with calcium and vitamin D. Efficacy of different doses and time intervals of oral vitamin D supplementation with or without calcium in elderly nursing home residents Vitamin D and Calcium Attenuate Bone Loss With Antiretroviral Therapy Initiation Vitamin D supplementation has minor effects on parathyroid hormone and bone turnover markers in vitamin D-deficient bedridden older patients. Prediction of bone mass density variation by bone remodeling markers in postmenopausal women with vitamin D insufficiency treated with calcium and vitamin D supplementation. Effects of a Multispecies Probiotic Supplement on Bone Health in Osteopenic Postmenopausal Women: A Randomized, Double-blind, Controlled Trial Long-term effects of nutrient intervention on markers of bone remodeling and calciotropic hormones in late-postmenopausal women. Does vitamin D supplementation of healthy Danish Caucasian girls affect bone turnover and bone mineralization? A global study of vitamin D status and parathyroid function in postmenopausal women with osteoporosis: baseline data from the multiple outcomes of raloxifene evaluation clinical trial. Effect of vitamin D supplementation on vitamin D status and bone turnover markers in young adults A randomised, controlled comparison of different calcium and vitamin D supplementation regimens in elderly women after hip fracture: The Nottingham Neck of Femur (NONOF) Study. Vitamin D Is a Major Determinant of Bone Mineral Density at School Age Serum ionized calcium, intact PTH and novel markers of bone turnover in bedridden elderly patients. Hypovitaminosis D and 'functional hypoparathyroidism'-the NoNoF (Nottingham Neck of Femur) study. The effect of high-dose vitamin D on bone mineral density and bone turnover markers in postmenopausal women with low bone mass—a randomized controlled 1-year trial The decline in hip bone density after gastric bypass surgery is associated with extent of weight loss. Effect of a Nutritional Supplementation on Bone Health in Chilean Elderly Subjects with Femoral Osteoporosis Calcium supplementation suppresses bone turnover during weight reduction in postmenopausal women. Effects of school meals with weekly fish servings on vitamin D status in Danish children: secondary outcomes from the OPUS (Optimal well-being, development and health for Danish children through a healthy New Nordic Diet) School Meal Study
Abstract : Vitamin D status is known to be an important determinant of bone mineral density ( BMD ) . There is a significant seasonal variation in serum vitamin D , and some studies have reported an associated seasonal variation in BMD . The present study was devised to investigate whether a seasonal variation in BMD could be detected in healthy normal subjects , along with associated variations in serum parathyroid hormone ( PTH ) , intestinal calcium absorption and biochemical markers of bone turnover . A second aim was to investigate whether , if such variations were identified , they could be suppressed by vitamin D supplementation . The subjects were 70 healthy female volunteers ( mean age 47.2 years , range 24–70 years ) recruited into a double-masked crossover study and followed over 2 years . During the first year 35 subjects received a daily oral supplement containing 800 IU ( 20 mg ) cholecalciferol ( group 1 ) and 35 subjects received a placebo preparation ( group 2 ) . During the second year the treatment each group received was reversed . Lumbar spine ( L1–L4 ) , left proximal femur and total body BMD were measured by DXA at 3-month intervals . Serum 25-hydroxyvitamin D ( 25-OHD ) , serum PTH , bone markers ( bone-specific ALP ( BSAP ) and urinary crosslinks ( DYPD/creatinine ) ) and calcium absorption were also measured at each visit . Cholecalciferol treatment increased serum 25-OHD by 25.4 nmol/l ( p < 0.001 ) , while a reciprocal decrease in serum PTH of 6.6 ng/l ( p = 0.011 ) was seen in subjects in the lowest quartile of baseline serum 25-OHD . The treatment had no significant effect on spine , femur or total body BMD , calcium absorption or bone markers . When Fourier analysis was used to analyze the data for seasonal effect ( defined as twice the amplitude of the 1-year period variation ) a highly significant effect for 25-OHD of 18 nmol/l ( p < 0.001 ) was found . However , no effect was found for BMD , PTH , calcium absorption or bone markers . The analysis set a 95 % confidence limit to the seasonal effect of less than 0.6 % for spine , total hip and total body BMD . It was concluded that in the population of healthy women studied there was no evidence of seasonal variation in spine , femur or total body BMD , serum PTH , calcium absorption or bone markers .  Vitamin D supplementation was found to have no effect on BMD BACKGROUND We conducted a r and omized , placebo-controlled , double-blind trial to test the hypothesis that vitamin D(3 ) supplementation would prevent bone loss in calcium-replete , African American postmenopausal women . METHODS Two hundred eight healthy black postmenopausal women , 50 to 75 years of age , were assigned to receive either placebo or 20 microg/d ( 800 IU ) of vitamin D(3 ) . Calcium supplements were provided to ensure a total calcium intake of 1200 to 1500 mg/d . After 2 years , the vitamin D(3 ) dose was increased to 50 microg/d ( 2000 IU ) in the active group , and the study continued for an additional year . Bone mineral density ( BMD ) was measured every 6 months . Markers of bone turnover , vitamin D metabolites , and parathyroid hormone ( PTH ) levels were measured in serum . RESULTS There were no significant differences in BMD between the active and control groups throughout the study . There was also no relationship between serum 25-hydroxyvitamin D levels attained and rates of bone loss . There was an increase in BMD of the total body , hip , and radius at 1 year in both groups . Over the 3 years , BMD declined at these sites by 0.26 % to 0.55 % per year . The BMD of the lumbar spine increased slightly in the placebo and active groups . There were no persistent changes in serum PTH levels or the markers of bone turnover , although there was a transient decline in PTH in both groups at 3 months . No significant adverse events were attributed to vitamin D supplementation . CONCLUSIONS There was no observed effect of vitamin D(3 ) supplementation on bone loss or bone turnover markers in calcium-replete , postmenopausal African American women . Further studies are needed to determine if these findings are applicable to women of other ethnic groups Summary The various factors that may contribute to vitamin D deficiency or insufficiency were examined among healthy Saudi pre- and postmenopausal women .  Vitamin D deficiency was highly prevalent among studied Saudi women with obesity , poor sunlight exposure , poor dietary vitamin D supplementation and age as the main risk factors . Introduction The various factors that may contribute to vitamin D deficiency or insufficiency in relation to bone health among Saudi women are not known . The main objectives of the present study were to determine the factors influencing  vitamin D status in relation to serum 25-hydroxyvitamin D ( 25(OH)D ) , intact parathyroid hormone ( PTH ) , bone turnover markers ( BTMs ) , bone mineral density ( BMD ) , and vitamin D receptor genotype ( VDR ) in healthy Saudi pre- and postmenopausal women . Methods A total number of 1,172 healthy Saudi women living in the Jeddah area were r and omly selected and studied .  Anthropometric parameters , socioeconomic status , sun exposure index together with serum levels of 25(OH)D , calcitriol , intact PTH , Ca , PO4 , Mg , creatinine , albumin , and biochemical BTMs were measured . BMD was measured by a dual energy X-ray absorptiometry and VDR genotypes were also determined . Results About 80.0 % of Saudi women studied exhibited vitamin D deficiency ( serum 25(OH)D < 50.0 nmol/L ) with only 11.8 % of all women were considered with adequate vitamin D status ( serum 25(OH)D > 75 nmol/L ) . Secondary hyperparathyroidism was evident in 18.5 % and 24.6 % in pre- and postmenopausal women with 25(OH)D < 50 nmol/L. Serum 25(OH)D was lower ( P < 0.001 ) and intact PTH higher ( P < 0.001 ) in the upper quintiles of body mass index ( BMI ) and waist-to-hip ratio ( WHR ) . Multiple linear regression analysis showed that BMI , sun exposure index , poor dietary vitamin D supplementation , WHR , and age were independent positive predictors of serum 25(OH)D values . Conclusions Vitamin D deficiency is highly prevalent among healthy Saudi pre- and postmenopausal women and largely attributed to obesity , poor exposure to sunlight , poor dietary vitamin D supplementation , and age INTRODUCTION Vitamin D status is considered as an important determinant of bone health but supplementation trials with vitamin D(3 ) have yielded conflicting results . The aim of this study was to investigate the associations between serum 25-hydroxyvitamin D ( 25-OH D ) , bone turnover markers , bone mineral density ( BMD ) , radius bone loss and incidence of fracture in postmenopausal women . METHODS 669 postmenopausal women ( mean age : 62.2 years ) belonging to a population -based cohort were followed prospect ively for a median of 11.2 years . At baseline , 25-OH D levels , BMD , bone turnover markers and clinical risk factors of osteoporosis were assessed . BMD loss at the radius was estimated by annual measurements of BMD and all incident fractures which occurred in 134 women were confirmed by radiographs . RESULTS 73 % and 35 % of women had serum 25-OH D levels below 75 and 50 nmol/l which correspond respectively to the median and lowest optimal values recently proposed for fracture prevention . 11 % of women had levels below 30 nmol/l . Serum 25-OH D correlated modestly with intact PTH ( r(2)=0.023 , p<0.0001 ) , but not with bone turnover markers or BMD at the hip and radius after adjustment for age . When levels of 25-OH D were considered as a continuous variable , there was no significant association between 25-OH D levels and radius BMD loss or fracture risk . After adjustment for age , there was no significant difference in incidence of fracture , BMD , radius BMD loss , bone turnover markers , grip strength and the percentage of fallers in the previous year between women with 25-OH D levels below or above 75 , 50 or 30 nmol/l . CONCLUSIONS In a population of home-dwelling healthy postmenopausal women with few of them with severe vitamin D deficiency , vitamin D status may not be an important determinant of bone health CONTEXT Effects of long-term calcium , with or without vitamin D , on  hip bone mineral density ( BMD ) and bone turnover in sunny climates have not been reported . OBJECTIVE The aim was to evaluate the effect of vitamin D added to calcium supplementation on hip dual-energy x-ray absorptiometry BMD and calcium-related analytes . DESIGN , SETTING , AND PARTICIPANTS The study was a 5-yr r and omized , controlled , double-blind trial of 120 community-dwelling women aged 70 - 80 yr . INTERVENTIONS The interventions were 1200 mg/d calcium with placebo vitamin D ( Ca group ) or with 1000 IU/d vitamin D2 ( CaD group ) , or double placebo ( control ) . MAIN OUTCOME MEASURES Hip BMD , plasma 25-hydroxyvitamin D , biomarkers of bone turnover , PTH , and intestinal calcium absorption were measured . RESULTS Hip BMD was preserved in CaD ( -0.17 % ) and Ca ( 0.19 % ) groups but not controls ( -1.27 % ) at yr 1 and maintained in the CaD group only at yr 3 and 5 . The beneficial effects were mainly in those with baseline 25-hydroxyvitamin D levels below the median ( 68 nmol/liter ) . At yr 1 , compared with controls , the Ca and CaD groups had 6.8 and 11.3 % lower plasma alkaline phosphatase , respectively ( P < or=0.02 ) , and 28.7 and 34.5 % lower urinary deoxypyridinoline to creatinine ratio , respectively ( P < or=0.05 ) . At 5 yr , this suppression was maintained only in the CaD group . CaD reduced PTH at 3 and 5 yr cf . controls ( 27.8 and 31.3 % , P < or=0.005 ) in those with baseline PTH levels above the median ( 3.6 pmol/liter ) . Therapy did not affect intestinal calcium absorption at high carrier loads . CONCLUSIONS Addition of vitamin D to calcium has long-term beneficial effects on bone density in elderly women living in a sunny climate , probably mediated by a long-term reduction in bone turnover rate Although there have been several studies of the effect of vitamin D status on bone turnover in the elderly , the findings are unclear , and , furthermore , to date very few have investigated this in young adults . The objective of these r and omized , placebo-controlled , double-blind , 2-center intervention studies was to investigate the effect of cholecalciferol supplementation ( 0 , 5 , 10 , and 15 microg cholecalciferol/d ) throughout winter time on indices of vitamin D status and bone turnover in young ( aged 20 - 40 y ; n = 215 ) and elderly ( aged > or = 64 y ; n = 204 ) adults , with relatively high mean calcium intakes of 976 and 874 mg/d , respectively .  Fasting serum concentrations of 25-hydroxyvitamin D [ 25(OH)D ] , parathyroid hormone ( PTH ) , osteocalcin , bone-specific alkaline phosphatase , and carboxyterminal collagen crosslinks were measured by enzyme immunoassays at baseline and endpoint . Fok I and Taq I vitamin D receptor ( VDR ) genotypes were determined by real-time PCR . Endpoint serum 25(OH)D increased ( P < 0.0001 ) in a dose-related manner with increasing supplemental cholecalciferol ( up to 15 microg/d ) in 20 - 40-y olds and up to 10 microg/d in > or = 64-y olds . Endpoint serum PTH was lower ( P < 0.05 ) in the 3 cholecalciferol-supplemented groups compared with that in the placebo group in > or = 64-y olds , but cholecalciferol supplementation did not affect other markers in either cohort and there was no significant interaction with VDR genotype . In conclusion , cholecalciferol supplementation alone throughout winter did not affect bone turnover markers in apparently healthy young and elderly adults , even when stratified by VDR genotype Levendo&U01E7;lu F , U&U01E7;urlu H , Gürbilek M , Akkurt E , Karagözo&U01E7;lu E : Increased bone resorption in the proximal femur in patients with hemiplegia . Am J Phys Med Rehabil 2004;83:835–841 . Objectives : To investigate the relationship between the proximal femoral bone mineral density and bone resorption markers , determinants of calcium metabolism and vitamin D levels in elderly stroke patients . Design : A total of 80 patients and 20 controls were enrolled in the study .  Bone mineral density measurements were obtained at the proximal femur . In all subjects ,  25-hydroxyvitamin D , 1,25-dihydroxyvitamin D , intact parathyroid hormone , osteocalcin , deoxypyridinoline , and ionized calcium concentrations  were measured . Barthel Index and Motricity Index Leg Score were recorded all patients . Results : The serum concentrations of deoxypyridinoline , intact parathyroid hormone , and the mean serum ionized calcium levels were significantly higher in patients with stroke than that of the control subjects . The mean serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D concentrations in patients were significantly lower than those of the control group ( P < 0.05 ) . The bone mineral density of proximal femurs of paretic limbs was decreased significantly compared with those of the control group ( P < 0.05 ) . There were significant correlations between the Z score of the hemiplegic side and the patients ’ Barthel Index , Motricity Index Leg Score , 25-hydroxyvitamin D , 1,25-dihydroxyvitamin D , calcium , and deoxypyridinoline . Conclusions : This study provides clear evidence that decreased mobility , vitamin D status , and bone turnover variables in patients after stroke are important factors in the greater bone loss in the paretic leg Low levels of 25-hydroxyvitamin D ( 25OHD ) are associated with increased bone turnover and risk of fractures . Plasma 25OHD is inversely related to body mass index , and vitamin D deficiency is common in obesity . We aim ed to determine whether vitamin D supplementation affects bone turnover and bone mineral density ( BMD ) in obese subjects . Fifty-two healthy obese men and women aged 18–50 years with plasma 25OHD levels below 50 nmol/L were r and omized to 7,000 IU of cholecalciferol daily or placebo for 26 weeks . We measured plasma levels of 25OHD , parathyroid hormone ( PTH ) , and markers of bone turnover , as well as BMD at the hip , spine , forearm , and whole body . Compared with placebo , treatment with cholecalciferol  increased mean plasma 25OHD from 35 to 110 nmol/L ( p < 0.00001 ) and significantly decreased PTH ( p < 0.05 ) . BMD increased significantly at the forearm by 1.6 ± 0.7 % ( p = 0.03 ) . The bone resorption marker C-terminal telopetide of type 1 collagen ( CTX ) decreased borderline significantly in the cholecalciferol group compared with the placebo group ( p = 0.07 ) . Changes in plasma 25OHD correlated inversely with changes in plasma levels of bone-specific alkaline phosphatase ( r = −0.38 , p = 0.01 ) and CTX ( r = −0.33 , p = 0.03 ) . Changes in CTX correlated inversely with changes in spine BMD ( r = −0.45 , p = 0.04 ) . Increasing circulating 25OHD levels by cholecalciferol treatment is of importance to bone health in young obese subjects as increased levels of 25OHD are associated with a decrease in both PTH and bone turnover and with an increase in BMD at the forearm Objectives The role vitamin D intake/production plays in sarcoidosis-associated hypercalcaemia is uncertain . However , authoritative review s have recommended avoiding sunlight exposure and vitamin D supplements , which might lead to adverse skeletal outcomes from vitamin D insufficiency . We investigated the effects of vitamin D supplementation on surrogate measures of skeletal health in patients with sarcoidosis and vitamin D insufficiency . Design R and omised , placebo-controlled trial . Setting Clinical research centre . Participants 27 normocalcaemic patients with sarcoidosis and 25-hydroxyvitamin D ( 25OHD ) < 50 nmol/L. Intervention 50 000 IU weekly cholecalciferol for 4 weeks , then 50 000 IU monthly for 11 months or placebo . Primary and secondary outcome measures The primary endpoint was the change in serum calcium over 12 months , and secondary endpoints included measurements of calcitropic hormones , bone turnover markers and bone mineral density ( BMD ) . Results The mean age of participants was 57 years and 70 % were women . The mean ( SD ) screening 25OHD was 35 ( 12 ) and 38 ( 9 ) nmol/L in the treatment and control groups , respectively . Vitamin D supplementation increased 25OHD to 94 nmol/L after 4 weeks , 84 nmol/L at 6 months and 78 nmol/L at 12 months , while levels remained stable in the control group . 1,25-Dihydroxy vitamin D levels were significantly different between the groups at 4 weeks , but not at 6 or 12 months . There were no between-groups differences in albumin-adjusted serum calcium , 24 h urine calcium , markers of bone turnover , parathyroid hormone or BMD over the trial . One participant developed significant hypercalcaemia after 6 weeks ( total cholecalciferol dose 250 000 IU ) . Conclusions In patients with sarcoidosis and 25OHD < 50 nmol/L  , vitamin D supplements did not alter average serum calcium or urine calcium , but had no benefit on surrogate markers of skeletal health and caused one case of significant hypercalcaemia . Trial registration This trial is registered at the Australian New Zeal and Clinical Trials Registry ( http://www.anzctr.org.au ) . The registration number is ACTRN12607000364471 , date of registration 5/7/2007 The objective of this study was to characterize changes in metabolic bone parameters following bariatric surgery .  Seventy-three obese adult patients who underwent either gastric b and ing ( GB ) , Roux-en-Y gastric bypass ( RYGB ) , or biliopancreatic diversion with duodenal switch ( BPD/DS )  were followed prospect ively for 18 months postoperatively . Changes in the calcium-vitamin D axis ( 25-hydroxyvitamin D ( 25OHD ) , 1,25-dihydroxyvitamin D ( 1,25(OH)(2)D ) , calcium , parathyroid hormone ( PTH ) ) , markers of bone formation ( osteocalcin , bone-specific alkaline phosphatase ) and resorption ( urinary N-telopeptide ( NTx ) ) , as well as bone mineral density ( BMD ) were assessed at 3-month intervals during this time period . Bariatric surgery result ed in significant and progressive weight loss over 18 months . With supplementation , 25OHD levels increased 65.3 % ( P < 0.0001 ) by 3 months , but leveled off and decreased < 30 ng/ml by 18 months . PTH initially decreased 21.4 % ( P = 0.01 ) at 3 months , but later approached presurgery levels . 1,25(OH)(2)D increased significantly starting at month 12 ( 50.3 % increase from baseline , P = 0.008 ) , and was positively associated with PTH ( r = 0.82 , P = 0.0001 ) . When stratified by surgery type , median PTH and 1,25(OH)(2)D levels were higher following combined restrictive and malabsorptive operations ( RYGB and BPD/DS ) compared to GB . Bone formation/resorption markers were increased by 3 months ( P < 0.05 ) and remained elevated through 18 months . Radial BMD decreased 3.5 % by month 18 , but this change was not significant ( P = 0.23 ) . Our findings show that after transient improvement , preoperative vitamin D insufficiency and secondary hyperparathyroidism persisted following surgery despite supplementation . Postoperative secondary hyperparathyroidism was associated with increased 1,25(OH)(2)D levels and increased bone turnover markers Black women have lower serum 25-hydroxyvitamin D ( 25[OH]D ) levels and higher parathyroid hormone ( PTH ) levels than white peers but lower bone turnover , suggesting skeletal resistance to PTH . Our objective was to determine if vitamin D supplementation ( 1,000 IU/day ) would prevent bone loss and whether vitamin D receptor ( VDR ) polymorphisms modify the response . We performed a 2-year r and omized , controlled , double-blind study of 1,000 IU vitamin D3 vs. placebo in postmenopausal black women with serum 25(OH)D levels < 20 ng/mL ( n = 103 ) .  Measurements of 25(OH)D , PTH , and bone turnover were evaluated at baseline and 3 , 6 , 12 , 18 , and 24 months . DNA was extracted from peripheral blood leukocytes , and genotyping was conducted using st and ard techniques . Spine and hip bone mineral density ( BMD ) was measured at baseline and every 6 months . Serum 25(OH)D increased 11 ng/mL with vitamin D supplementation ( p < 0.001 ) , with no change in the placebo group . Vitamin D supplementation produced a significant decline in PTH at 3 months only , with no differences in bone turnover between placebo and vitamin D at any time point . Two-year changes in BMD were not significantly different between placebo- and vitamin D-treated black women at any skeletal site . Despite similar elevations in 25(OH)D , femoral neck BMD was only responsive to vitamin D supplementation in FF subjects ( n = 47 ) , not Ff/ff subjects ( n = 31 ) . Vitamin D supplementation does not appear to influence  bone loss in black women . However , in the FF polymorphism of the VDR gene group , vitamin D supplementation may retard the higher rate of bone loss Patients with primary hyperparathyroidism ( PHPT ) have higher bone turnover , lower bone mineral density ( BMD ) , and an increased risk of fractures . They also have a high incidence of low vitamin D levels ( 25-OH-vitamin D < 50 nmol/L ) that could worsen the negative effect on the bone . In this double-blinded clinical trial , 150 patients with PHPT were r and omized , after successful parathyroidectomy ( PTX ) , to 1-year daily treatment with either cholecalciferol 1600 IU and calcium carbonate 1000 mg ( D+ ) or calcium carbonate alone ( D- ) . BMD was measured in the lumbar spine , femoral neck , total hip , distal and 33 % radius using dual-energy X-ray absorptiometry ( DXA ) before surgery and after 1 year of study medication . Median age was 60 ( range 30 - 80 ) years and there were 119 ( 79 % ) women and 31 ( 21 % ) men ; 76 % had 25-OH-D < 50 nmol/L before PTX and 50 % had persistent elevated parathyroid hormone ( PTH ) 6 weeks after PTX . A similar increase in BMD in the lumbar spine , femoral neck , and total hip was observed in both groups ( D+ : 3.6 % , 3.2 % , and 2.7 % , p<0.001 , respectively ; and D- : 3.0 % , 2.3 % , and 2.1 % , respectively , p<0.001 ) . Patients with vitamin D supplementation also increased their BMD in distal radius ( median 2.0 % ; interquartile range , -1.7 % to 5.4 % ; p=0.013 ) . The changes in BMD , especially in the hips , were correlated to the baseline concentrations of PTH , ionized calcium , and bone markers ( p<0.001 ) . A benefit from vitamin D substitution was observed among patients with a persistent postoperative PTH elevation , who also improved their BMD at 33 % radius and radius ultradistal ( p<0.05 ) . In conclusion , except for a minor improvement of radius BMD , our data show no beneficial effect on BMD or bone turnover markers of vitamin D supplementation after PTX . Preoperative PTH seems to have the strongest association with improvement in BMD To examine the relation of the vitamin D status and the remaining estrogen activity with bone turnover and bone mineral density ( BMD ) in elderly women , BMD was measured at both hips using dual-energy X-ray absorptiometry and at the distal radius using single photon absorptiometry , in 330 healthy women aged 70 and over .  Vitamin D metabolites , sex hormone binding globulin ( SHBG ) , PTH(1 - 84 ) , osteocalcin , alkaline phosphatase , and hydroxyproline and calcium excretion in 2 h fasting urine were measured . Multiple linear regression was used to adjust for potential confounders . In 65 % of the women , serum 25(OH)D was below 30 nmol/l . Only values below a threshold for 25(OH)D were negatively related to serum PTH(1 - 84 ) ( p = 0.02 , threshold at 25 nmol/l ) and to osteocalcin levels ( p = 0.04 , threshold at 30 nmol/l ) . BMD of the femoral neck and trochanter was positively related to serum 25(OH)D ( left neck p = 0.001 ) with thresholds at 30 nmol/l whereas the distal radius was not ( p = 0.32 ) . Serum PTH was negatively related to BMD at all measurement sites ( all p < 0.001 ) . Serum SHBG , an inverse measure of estrogen activity , was positively related to osteocalcin levels ( p = 0.004 ) and the urinary hydroxyproline/creatinine ratio ( p = 0.002 ) and negatively related to the BMD of the trochanter ( left trochanter p = 0.02 ) and the distal radius ( p = 0.001 ) . We conclude that in elderly women , serum 25(OH)D levels below 30 nmol/l are associated with secondary hyperparathyroidism and increased bone turnover . SHBG is positively related to bone turnover . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Low-energy fractures of the hip , forearm , shoulder , and spine are known consequences of osteoporosis . OBJECTIVE We evaluated the effect of 1 y of treatment with calcium and vitamin D on bone mineral density ( BMD ) and bone markers in patients with a recent low-energy fracture . DESIGN In a double-blinded design , patients with fracture of the hip ( lower-extremity fracture , or LEF ) or upper extremity ( UEF ) were r and omly assigned to receive 3000 mg calcium carbonate + 1400 IU cholecalciferol or placebo ( 200 IU cholecalciferol ) . BMD of the hip ( HBMD ) and lumbar spine ( LBMD ) were evaluated by dual-energy X-ray absorptiometry , and physical performance was assessed by the timed Up & Go test . Serum concentrations of 25-hydroxycholecalciferol , parathyroid hormone ( PTH ) , telepeptide of type I collagen ( ICTP ) , osteocalcin , and N-terminal propeptide of collagen type I were measured . RESULTS A total of 122 patients were included ( 84 % women ; x + /- SD age : 70 + /- 11 y ) ; 68 % completed the study . In an intention-to-treat analysis , LBMD increased in the intervention group and decreased in the placebo group , and the difference between the groups was significant after 12 mo : 0.931 + /- 0.211 compared with 0.848 + /- 0.194 ( P<0.05 ) . No significant change was shown for HBMD . The effect of treatment was more pronounced in patients aged < 70 y. The intervention decreased bone turnover . PTH was significantly lower in the intervention group ( P<0.01 ) for the LEF patients . ICTP and change in LBMD were significantly related to physical performance . CONCLUSIONS A 1-y intervention with calcium and vitamin D reduced bone turnover , significantly increased BMD in patients younger than 70 y , and decreased bone loss  in older patients . The effect of treatment was related to physical performance Summary The effect of equivalent oral doses of vitamin D3 600 IU/day , 4200 IU/week and 18,000 IU/month on vitamin D status was compared in a r and omized clinical trial in nursing home residents . A daily dose was more effective than a weekly dose , and a monthly dose was the least effective . Introduction It is assumed that equivalent daily , weekly or monthly doses of vitamin D3 equally influence vitamin D status . This was investigated in a r and omized clinical trial in nursing home residents . Methods The study was performed in ten nursing homes including 338 subjects ( 76 male and 262 female ) , with a mean age of 84 ( ± SD 6.3 years ) . They received oral vitamin D3 either 600 IU/day , or 4200 IU/week , or 18,000 IU/month or placebo . After 4 months , calcium was added during 2 weeks , 320 mg/day or 640 mg/day or placebo . Outcome : serum levels of 25-hydroxyvitamin D ( 25(OH)D ) , parathyroid hormone ( PTH ) and bone turnover markers . Statistical approach : linear multilevel analysis . Results At baseline , mean serum 25(OH)D was 25.0 nmol/L ( SD 10.9 ) , and in 98 % , it was lower than 50 nmol/L. After 4 months , mean serum 25(OH)D levels increased to 62.5 nmol/L ( after daily vitamin D3 69.9 nmol/L , weekly 67.2 nmol/L and monthly 53.1 nmol/L , P < 0.001 between groups ) . Median serum PTH levels decreased by 23 % ( p < 0.001 ) . Bone turnover markers did not decrease . Calcium supplementation had no effect on serum PTH and bone turnover . Conclusion Daily vitamin D was more effective than weekly , and monthly administration was the least effective Context Patients with HIV who initiate antiretroviral therapy ( ART ) lose bone mineral density ( BMD ) . The role of supplementation with vitamin D and calcium in preventing such loss is unknown . Contribution In a r and omized clinical trial of patients with HIV who were initiating ART , BMD , 25-hydroxyvitamin D , parathyroid hormone , phosphate metabolism , and markers of bone turnover were measured at baseline . Patients who then received vitamin D3 plus calcium along with ART had smaller declines in BMD of the hip and spine than those who received placebo along with ART . Caution Nearly all of the patients were men . Implication Supplementation with vitamin D and calcium may prevent bone loss  in patients with HIV initiating ART .  Antiretroviral therapy ( ART ) has transformed HIV infection from a terminal disease to a manageable chronic illness . Although incidence of AIDS-defining conditions has decreased , it has increased for other comorbid conditions ( 1 ) , including osteoporosis and fragility fractures ( 27 ) . Both viral and host factorsHIV infection mediated by certain viral proteins , HIV-associated inflammation , lifestyle and behavioral factors , underlying genetic predisposition , comorbid conditions , and ARTprobably contribute to bone loss and fracture risk ( 814 ) . Studies of ART initiation have confirmed that 2 % to 6 % of hip and spine BMD is lost over the first 24 to 48 weeks after initiation , with subsequent stabilization ( 1518 ) . The magnitude of bone loss is similar to that seen with glucocorticoids or during the first year of menopausal transition ( 19 , 20 ) . Initial loss is marked by an increase in serum bone resorption markers followed by a delayed compensatory increase in bone formation markers ( 21 ) ; therefore , this catabolic window , a high bone turnover state with excess resorption , may be a central mechanism of bone loss with ART initiation . Tenofovir disoproxil fumarate ( TDF ) , a nucleotide analogue reverse transcriptase inhibitor , has been associated with greater bone loss than other reverse transcriptase inhibitors ( 15 , 16 ) . Use of TDF is associated with increased parathyroid hormone ( PTH ) , elevated vitamin D binding protein , and reduced free 1,25-dihydroxyvitamin D [ 1,25-(OH)2D3 ] levels ( 22 , 23 ) , suggesting that functional vitamin D deficiency with TDF use potentially contributes to excess bone loss . Initiation of efavirenz ( EFV ) , a nonnucleoside reverse transcriptase inhibitor , is associated with a 6.2- to 12.5-nmol/L decrease in 25-hydroxyvitamin D [ 25-(OH)D ] levels ( 24 , 25 ) . Efavirenz induces cytochrome P450 enzymes involved in vitamin D metabolism and may accelerate the catabolism of 25-(OH)D and 1,25-(OH)2D3 , the latter being the active vitamin D metabolite ( 26 ) . These ART agents are combined with emtricitabine ( FTC ) , a nucleoside analogue reverse transcriptase inhibitor , into a fixed-dose combination , once-a-day pill ( EFV/FTC/TDF ) that is highly effective for treating HIV ( 27 ) . Beyond effects on bone metabolism , vitamin D has immunomodulatory effects mediated through the vitamin D receptor present on cells in both the innate and the adaptive immune system ( 28 , 29 ) . Vitamin D increases monocyte expression of CD14 and cathelicidin , molecules involved in innate immune responses ( 30 , 31 ) ; down-regulates cytokine expression in activated T cells ; and suppresses T-cell proliferation and production of interferon- and interleukin (IL)-2 , thus reducing the net state of inflammation ( 32 , 33 ) . These pathways are particularly relevant in HIV infection , in which excess monocyte and T-cell activation are important drivers of morbidity and mortality ( 3437 ) . We hypothesized that high-dose vitamin D and calcium supplementation would attenuate bone loss associated with initiation of EFV/FTC/TDF . In addition , we evaluated immunomodulatory effects of vitamin D in the setting of HIV treatment . We report the results of the AIDS Clinical Trials Group A5280 trial , a multicenter , r and omized , double-blind , placebo-controlled study assessing the effect of daily oral doses of 4000 IU of vitamin D3 and 1000 mg of calcium carbonate in adults with HIV initiating their first ART regimen with EFV/FTC/TDF . Methods Patients with ART-naive HIV without evidence of resistance to the antiretrovirals in the regimen and with HIV-1 RNA levels greater than 1000 copies/mL were eligible if they met the following criteria : screening 25-(OH)D level between 25 and 188 nmol/L ; creatinine clearance of 60 mL/min/1.73 m2 or greater , estimated by the CockcroftGault formula ; and serum calcium level less than 2.6 mmol/L. We excluded patients with daily calcium supplementation greater than 500 mg , daily vitamin D supplementation greater than 800 IU , any bisphosphonate use , recent steroid or chemotherapy treatments , clinical ly active thyroid disease , active substance or alcohol abuse , history of fragility fracture , documented osteoporosis , nephrolithiasis , or weight greater than 136 kg ( limit of the dual-energy x-ray absorptiometry [ DXA ] scanner ) . Pregnant and breastfeeding women were also excluded . We did 3-day dietary recalls at entry to estimate vitamin D and calcium intake . Patients were r and omly assigned to 4000 IU of cholecalciferol ( vitamin D3 ) daily plus 500 mg of calcium carbonate twice daily or identically matching placebos ( Tishcon ) and were counseled to take with food to facilitate absorption . Some experts consider the current upper U.S. Dietary Reference Intake of 2000 IU to be below actual physiologic requirements ; therefore , we tested the highest supplementation without risk for toxicity ( 3840 ) . A dose of 4000 IU of vitamin D3 is the highest daily dose considered safe for adults by the Institute of Medicine ( 41 ) and has previously been evaluated in persons with HIV with excellent tolerability and safety data ( 42 ) . Patients were r and omly assigned in a 1:1 ratio using permuted blocks stratified by screening serum 25-(OH)D levels ( 50 and > 50 nmol/L ) . R and omization was done using Web-based access to a central computer system maintained by the Frontier Science & Technology Research Foundation ( Buffalo , New York ) . The institutional review boards of all participating sites approved the study , and all patients provided written informed consent . The primary end point was percentage of change in total hip BMD from baseline to 48 weeks . Secondary end points included percentage of change in lumbar spine BMD at 48 weeks , change in plasma 25-(OH)D and PTH levels , markers of bone turnover , soluble inflammatory biomarkers , and CD4 cell counts at 24 and 48 weeks . Incidence of hypercalcemia and nephrolithiasis was monitored . All DXA scans were read in a blinded fashion at the Body Composition Analysis Center at Tufts Medical Center ( Boston , Massachusetts ) using a st and ardized protocol . Biomarker Assays Screening was done at local laboratories certified by the Clinical Laboratory Improvement Amendments . Serum sample s were stored at 70C at the Irving Institute Biomarkers Core Laboratory at Columbia University Medical Center ( New York , New York ) and underwent batched analysis . We measured 25-(OH)D2 and 25-(OH)D3 by liquid chromatographymass spectrometry , intact PTH by a radioimmunoassay ( Scantibodies ) , procollagen-1 N-terminal peptide ( P1NP ) by a radioimmunoassay ( Immunodiagnostic Systems ) , C-terminal telopeptide of type 1 collagen ( CTX ) by an enzyme-linked immunosorbent assay [ ELISA ] ( Immunodiagnostic Systems ) , IL-6 by an ELISA ( R&D Systems ) , soluble tumor necrosis factor receptor ( sTNFR ) by an ELISA ( R&D Systems ) , and soluble CD14 by an ELISA ( R&D Systems ) . Inflammatory biomarkers were chosen based on association with relevant end points ( 4346 ) . All biomarkers , except for 25-(OH)D , were measured in duplicate , and values were averaged for analysis . Statistical Analysis To provide an intention-to-treat analysis , evaluations were done regardless of treatment change or discontinuation . Two patients who did not have the correct vitamin D test done at baseline were excluded from the efficacy analyses . Stratified Wilcoxon rank-sum tests were used to evaluate for distribution shifts between the treatment groups , which were stratified by screening vitamin D levels . Fisher exact tests and Wilcoxon rank-sum tests were used to evaluate for differences between groups for categorical and continuous secondary outcomes , respectively . Wilcoxon signed-rank tests were used to evaluate change within a treatment group . The 95 % CIs for median changes within a group were estimated using a distribution-free method via percentiles . For the BMD outcomes , modification of the treatment effect by screening vitamin D stratum was evaluated by means of linear regression . Analyses of the primary outcomes of change in hip and spine BMD from baseline to 48 weeks used a multiple-imputation approach to fill in missing data with a Markov-chain Monte Carlo method . A prespecified complete-case approach was used for analyses by stratum and to assess interactions . Five imputations were used , based on screening 25-(OH)D strata , age , sex , and race/ethnicity . All statistical tests were 2-sided and interpreted at the 5 % nominal level of significance without adjustment for multiple comparisons . Analyses were done using the FREQ , UNIVARIATE , REG , MI , and MIANALYZE procedures in SAS , version 9.2 ( SAS Institute ) , and STRATIFY and PAIRED procedures in Proc-StatXact , version 9 ( Cytel ) . Role of the Funding Source The National Institute of Allergy and Infectious Diseases funded the study . Industry sponsors ( Bristol-Myers Squibb , Gilead Science , and Tishcon ) provided antiretrovirals , vitamin D , calcium , and matching placebos , and additional funding was provided for completion of DXA scans and laboratory assays . The National Institute of Allergy and Infectious Diseases had no role in the design and conduct of the study ; collection , management , analysis , or interpretation of the data ; preparation , review , or approval of the manuscript ; or decision to su bmi t the manuscript for publication . The manuscript was review ed by OBJECTIVES to evaluate the effects of vitamin D supplementation on parathyroid function and bone turnover in aged , chronically immobile patients . DESIGN a r and omised double-blind controlled trial . SUBJECTS two hundred and eighteen long-term in patients aged over 65 years . INTERVENTION the patients were r and omised into treatment groups of I-III , each receiving 0 IU , 400 IU and 1200 IU cholecalciferol per day , respectively . In case of inadequate consumption of dairy products , patients received a daily calcium substitution of 500 mg . MEASUREMENTS plasma concentrations of 25-hydroxyvitamin D ( 25-OHD ) , intact parathyroid hormone ( PTH ) , amino-terminal propeptide of type I procollagen ( PINP ) , a marker of bone formation , and carboxy-terminal telopeptide of type I collagen ( ICTP ) , a marker of bone resorption , were measured at baseline and after 6 months . RESULTS the patients ( age 84.5 years ) were chronically bedridden . The baseline 25-OHD was low ( 23 nmol/l ) , correlated inversely with PINP , and tended to associate inversely with PTH . The prevalence of vitamin D deficiency ( VDD ) ( 25-OHD < 50 nmol/l ) was 98 % and PTH was elevated in 23 % of the patients . Vitamin D supplementation significantly increased 25-OHD concentrations ( 124 % group II , 204 % group III ) and decreased PTH ( -7 % group II , -8 % group III ) . PINP tended to decrease , but ICTP tended to increase , and only their ratio decreased significantly . The tendency of ICTP to increase was inconsistent . Changes in 25-OHD correlated inversely with those in PTH and PINP . CONCLUSIONS vitamin D supplementation has minor effects on PTH and bone turnover in chronically immobilised aged patients with VDD . Further comparative studies and meta-analyses are warranted to eluci date the confounding effects of different mobility levels on the benefits of vitamin D supplementation in patients with differing baseline PTH levels The aim of this study was to determine whether early changes in bone markers could predict long-term response in bone mineral density ( BMD ) after calcium ( 500 mg ) and vitamin D ( 400 IU ) supplementation twice daily in ambulatory elderly women with vitamin D insufficiency ( 25-hydroxyvitamin D , < 12 ng/ml ) . One hundred and ninety-two women ( mean age , 75 + /- 7 yr ) were r and omized to receive either the supplementation ( n = 95 ) or a placebo ( n = 97 ) in a double-blind , controlled clinical trial for 1 yr . In comparison with the placebo group , supplementation significantly increased BMD , normalized 25-hydroxyvitamin D and significantly decreased intact PTH and bone remodeling markers . The initial values of telopeptide cross-links were correlated with improvement in total body BMD [ urinary N-telopeptides ( NTX ) , r = 0.38 ; C-telopeptides ( CTX ) , r = 0.32 ; serum CTX , r = 0.28 ] , and the 3-month changes in the same markers were correlated with improvement in total body ( urinary N-telopeptides , r = -0.29 ; serum CTX , r = -0.26 ) and vertebral BMD ( CTX , r = -0.26 ; all P < 0.05 ) . We concluded that short-term changes in bone resorption markers can predict long-term variations in BMD in elderly women with vitamin D insufficiency receiving calcium  and vitamin D supplementation ABSTRACT Objective : The development of alternative approaches to prevent and /or treat osteoporosis , as a chronic progressive bone disease , is being considered currently . Among dietary supplements , probiotics may have favorable effects on bone metabolism . Therefore , the aim of this study was to evaluate the effects of a multispecies probiotic supplementation on bone biomarkers and bone density in osteopenic postmenopausal women . Methods : This r and omized double-blind placebo-controlled clinical trial was performed on 50 patients with osteopenia aged 50–72 years . Participants were r and omly assigned to take either a multispecies probiotic supplement ( GeriLact ; n = 25 ) or placebo ( n = 25 ) for 6 months . GeriLact contains 7 probiotic bacteria species . Participants received 500 mg Ca plus 200 IU vitamin D  daily . Bone mineral density ( BMD ) of lumbar spine and total hip and blood biomarkers including bone-specific alkaline phosphatase ( BALP ) , osteocalcin ( OC ) , collagen type 1 cross-linked C-telopeptide ( CTX ) , deoxypyridinoline ( DPD ) , parathyroid hormone ( PTH ) , 25-OH vitamin D , and serum pro-inflammatory cytokines ( tumor necrosis factor [TNF]-α and interleukin [IL]-1β ) were assessed at baseline and at the end of the study . Results : The multispecies probiotic significantly decreased BALP ( p = 0.03 ) and CTX ( p = 0.04 ) levels in comparison with the control group but had no effect on BMD of the spine and total hip . Moreover , there was a statistically significant decrease in serum PTH ( p = 0.01 ) and TNF-α ( p = 0.02 ) in the intervention group compared to the placebo group . Conclusions : These results may suggest the favorable effects of the multispecies probiotic supplementation for 6 months on bone health in postmenopausal women due to slowing down the rate of bone turnover BACKGROUND Adequate intakes of calcium and vitamin D reduce bone loss and fracture risk in the elderly . Other nutrients also affect bone health , and adequate intakes may influence bone turnover and balance . OBJECTIVE We compared the long-term effects on bone turnover markers and calciotropic hormones of a multinutrient supplement , a calcium and vitamin D supplement , and dietary instruction aim ed at increasing calcium intake through foods . DESIGN Ninety-nine healthy postmenopausal women participated in a 3-y , r and omized trial , receiving either 1 ) supplemental calcium ( 1450 mg/d ) and vitamin D [ 10 microg ( 400 IU)/d ] , 2 ) calcium , vitamin D , and other nutrients ( multinutrient supplement ) , or 3 ) dietary instruction ( dietary control group ) . Data are from 83 subjects who completed the trial . RESULTS Increases over baseline in calcium intakes and serum 25-hydroxyvitamin D concentrations were sustained over 3 y in all treatment groups . Circulating parathyroid hormone concentrations were reduced at year 1 in all treatment groups but trended toward baseline thereafter . Bone turnover markers followed a similar pattern , and none of the changes in biochemical concentrations differed significantly between groups . CONCLUSIONS All 3 interventions offer long-term feasibility for increasing calcium intake and serum 25-hydroxyvitamin D concentrations . The dietary addition of micronutrients implicated in skeletal physiology confers no obvious bone-sparing effect in healthy postmenopausal women beyond that of calcium and vitamin D alone . The attenuation over time in suppression of parathyroid hormone and bone turnover might help explain why nutrient intervention tends to have less of a bone-sparing effect than do skeletally active medications such as estrogen or bisphosphonates INTRODUCTION A high peak bone mass may be essential for reducing the risk of osteoporosis later in life and a sufficient vitamin D level during puberty may be necessary for optimal bone accretion and obtaining a high peak bone mass . Dietary intake and synthesis during winter of vitamin D might be limited but the effect of vitamin D supplementation in adolescence on bone mass is not well established . OBJECTIVE To investigate the effect of supplementation with 5 and 10 microg/day vitamin D(3 ) for 12 months in 11- to 12-year-old girls on  bone mass and bone turnover as well as the possible influence of VDR and ER genotype on the effect of the supplementation . METHODS The girls ( n=221 ) were r and omized to receive either 5 microg or 10 microg vitamin D(3 ) supplementation per day or placebo for 12 months . Whole body and lumbar spine bone mass measured by DXA and pubertal status were determined at baseline and after 12 months whereas physical activity and dietary intake of calcium and vitamin D were assessed at baseline . Serum ( S ) 25-hydroxyvitamin D ( 25OHD ) , S-osteocalcin , S-parathyroid hormone , S-calcium , S-inorganic phosphate , urinary ( U ) pyridinoline ( Pyr ) and deoxpyridinoline ( Dpyr ) were measured at baseline and after 6 and 12 months . RESULTS The S-25OHD concentration increased ( p<0.001 ) relative to the baseline values in the groups receiving either 5 microg/day ( mean+/-SD ; 11.0+/-10.3 nmol/l , baseline 41.9+/-17.6 nmol/l ) or 10 microg/day ( 13.3+/-11.8 nmol/l , baseline 44.4+/-16.6 nmol/l ) vitamin D(3 ) for 12 months compared to placebo ( -3.1+/-9.8 nmol/l , baseline 43.4+/-17.1 nmol/l ) . There was no effect of vitamin D-supplementation on biomarkers for bone turnover or on whole body or spine bone mineral augmentation . However , vitamin D supplementation increased whole body bone mineral density ( BMD ) ( p=0.007 ) and bone mineral content ( BMC ) ( p=0.048 ) in the FF VDR genotype but not in the Ff or ff VDR genotypes . CONCLUSION Supplementation with vitamin D ( 5 or 10 microg/day ) over 12 months increased the S-25OHD concentration but there was no effect on indices of bone health in the entire group of girls . However , there was an effect on BMD for a subgroup with the FF VDR genotype indicating an influence of genotype Vitamin D deficiency leads to secondary hyperparathyroidism , increased bone turnover , and bone loss and , when severe , to osteomalacia . Vitamin D deficiency is common in elderly people , especially the institutionalized . The definition of vitamin D deficiency is hampered by the fact that large interlaboratory differences exist in assays for serum 25-hydroxyvitamin D ( 25OHD ) , the main circulating metabolite . The international Multiple Outcomes of Raloxifene Evaluation study , a large prospect i ve intervention trial in postmenopausal women with osteoporosis , offered the opportunity to compare vitamin D status and parathyroid function throughout many countries over the world . For this study , baseline data were available from 7564 postmenopausal women from 25 countries on 5 continents . All women had osteoporosis , i.e. bone mineral density ( BMD ) at femoral neck or lumbar spine was lower than t-score -2.5 , or they had 2 vertebral fractures .  Serum 25OHD was measured by RIA , and  serum PTH  was measured by immunoradiometric assay .  BMD was measured by dual x-ray absorptiometry . The mean ( + /-SD ) serum 25OHD was 70.8 + /- 30.9 nmol/L. A low serum 25OHD ( < 25 nmol/L ) was observed in 4.1 % of all women in the Multiple Outcomes of Raloxifene Evaluation study , ranging from 0 % in south east Asia ( very few patients ) to 8.3 % in southern Europe . Serum 25OHD was between 25 - 50 nmol/L in 24.3 % of the women . Serum 25OHD showed a significant seasonal relationship , with lower values in all regions in winter . Serum PTH correlated negatively with serum 25OHD ( r = -0.25 ; P < 0.001 ) . This significant negative correlation was observed in all regions . When serum 25OHD was less than 25 , 25 - 50 , or more than 50 nmol/L , respectively , mean serum PTH levels were 4.8 , 4.1 , and 3.5 pmol/L , respectively ( by ANOVA , P < 0.001 ) . Similarly , mean alkaline phosphatase levels were 83.7 , 79.1 , and 75.7 U/L ( P < 0.001 ) , respectively , with increasing serum 25OHD . The effect of serum 25OHD on BMD was only significant for the BMD of the trochanter where a serum 25OHD level less than 25 nmol/L was associated with a 4 % lower BMD . After 6 months of treatment with vitamin D(3 ) ( 400 - 600 IU/day ) and calcium ( 500 mg/day ) , serum 25OHD increased from 70.8 + /- 29.8 to 92.3 + /- 28.6 nmol/L. Serum PTH decreased significantly after 6 months of treatment , and this decrease depended on baseline serum 25OHD . When baseline serum 25OHD was less than 25 , 25 - 50 , or more than 50 nmol/L , respectively , serum PTH decreased by 0.8 , 0.5 , or 0.2 pmol/L , respectively ( P < 0.001 ) . In conclusion , serum 25OHD was less than 25 nmol/L in 4 % of the women , and this was associated with a 30 % higher serum PTH . In 24 % of the women  serum 25OHD was between 25 - 50 nmol/L , associated with a 15 % higher level of serum PTH compared with women with a serum 25OHD greater than 50 nmol/L. A low serum 25OHD level was also associated with higher serum alkaline phosphatase and lower BMD of the trochanter . Treatment with vitamin D(3 ) and calcium increased serum 25OHD and decreased serum PTH significantly ; the effect was greater for lower baseline serum 25OHD Objective : To assess the vitamin D status of healthy young people living in Northern Irel and and the effect of vitamin D supplementation on vitamin D status and bone turnover . Design : Double-blinded r and omised controlled intervention study . Setting : University of Ulster , Coleraine , Northern Irel and .Subjects : In total , 30 apparently healthy students ( 15 male and 15 female subjects ) , aged 18–27 years , were recruited from the university , with 27 completing the intervention . Interventions : Subjects were r and omly assigned , to receive either 15 μg ( 600 IU ) vitamin D3 and 1500 mg calcium/day ( vitamin D group ) , or 1500 mg calcium/day ( control group ) for 8 weeks between January and March . Vitamin D status , bone turnover markers , serum calcium and parathyroid hormone concentrations were measured at baseline and post intervention . Results : At baseline , vitamin D status was low in both the vitamin D group ( 47.9 ( s.d . 16.0 ) ) and the control group ( 55.5 ( s.d . 18.6 ) nmol/l 25(OH)D ) . Post intervention vitamin D status was significantly higher in the vitamin D-treated group ( 86.5 ( s.d . 24.5 ) ) compared to the control group ( 48.3 ( s.d . 16.8 ) nmol/l ) ( P<0.0001 ) . There was no significant effect of supplementation on bone turnover markers or PTH concentrations . Conclusions : This study suggests that young adults in Northern Irel and do not consume an adequate daily dietary intake of vitamin D to maintain plasma vitamin D concentrations in the wintertime . A daily supplement of 15 μg vitamin D3 significantly increased vitamin D status in these individuals to levels of sufficiency . Achievement of an optimum vitamin D status among young adults may have future positive health implication BACKGROUND survivors of hip fracture are at 5- to 10-fold risk of a second hip fracture . There is little consensus about secondary prevention . Many are given calcium and vitamin D , but the evidence supporting this is circumstantial . OBJECTIVE to compare the effects of different calcium and vitamin D supplementation regimens on bone biochemical markers , bone mineral density and rate of falls in elderly women post-hip fracture . DESIGN r and omised controlled trial . SETTING orthogeriatric rehabilitation ward . METHODS 150 previously independent elderly women , recruited following surgery for hip fracture , were assigned to receive a single injection of 300,000 units of vitamin D(2 ) , injected vitamin D(2 ) plus 1 g/day oral calcium , 800 units/day oral vitamin D(3 ) plus 1 g/day calcium , or no treatment . Follow-up was one year , with measurement of 25-hydroxyvitamin D , parathyroid hormone , bone mineral density , and falls . RESULTS mean 25-hydroxyvitamin D increased and mean parathyroid hormone was suppressed in all the actively treated groups , more so in the group receiving combined oral vitamin D and calcium . Twenty per cent of participants injected with vitamin D were deficient in 25-hydroxyvitamin D a year later . Bone mineral density showed small but statistically significant differences of up to 4.6 % between actively treated groups and placebo . Relative risk of falling in the groups supplemented with vitamin D was 0.48 ( 95 % CI 0.26 - 0.90 ) compared with controls . CONCLUSION Vitamin D supplementation , either orally or with injected vitamin D , suppresses parathyroid hormone , increases bone mineral density and reduces falls . Effects may be more marked with calcium co-supplementation . The 300,000 units of injected vitamin D may not last a whole year Background Vitamin D insufficiency in children may have long-term skeletal consequences as vitamin D affects calcium absorption , bone mineralization and bone mass attainment . Methodology /Principal Findings This school-based study investigated vitamin D status and its association with vitamin D intake and bone health in 195 Finnish children and adolescents ( age range 7–19 years ) . Clinical characteristics , physical activity and dietary vitamin D intake were evaluated . Blood and urine sample s were collected for serum 25-hydroxyvitamin D ( 25-OHD ) and other parameters of calcium homeostasis . Bone mineral density ( BMD ) and body composition were measured with dual-energy X-ray absorptiometry ( DXA ) . Altogether 71 % of the subjects were vitamin D insufficient ( 25-OHD < 50 nmol/L ) . The median 25-OHD was 41 nmol/L for girls and 45 nmol/L for boys , and the respective median vitamin D intakes 9.1 µg/day and 10 µg/day . In regression analysis , after adjusting for relevant factors , 25-OHD concentration explained 5.6 % of the variance in lumbar BMD ; 25-OHD and exercise together explained 7.6 % of the variance in total hip BMD and 17 % of the variance in whole body BMD . S-25-OHD was an independent determinant of lumbar spine and whole body BMD and in magnitude surpassed the effects of physical activity . Conclusions / Significance Vitamin D insufficiency was common even when vitamin D intake exceeded the recommended daily intake . Vitamin D status was a key determinant of BMD . The findings suggest urgent need to increase vitamin D intake to optimize bone health in children Chronic immobilization could markedly affect calcium and bone metabolism in elderly people . To investigate this , and to test the theory of ' type II ' osteoporosis in bedridden elderly patients with low vitamin D status , 55 such subjects were examined .  Serum concentrations of ionized calcium ( Ca++ ) , intact parathyrin ( PTH ) and two novel markers of bone collagen formation ( carboxyterminal propeptide of type I procollagen ; PICP ) and resorption ( carboxyterminal crosslinked telopeptide of type I collagen ; ICTP ) were measured . The effects on these parameters after 40 weeks of supplementation with vitamin D ( 1000 IU d-1 ) and /or calcium ( 1 g d-1 ) were subsequently prospect ively evaluated . Despite low ( mean 11.6 nmoll-1 ) serum 25-hydroxyvitamin D levels ( 25-OHD ) , those of 1,25-dihydroxy-vitamin D ( 1,25-(OH)2D ) were mostly normal . Neither correlated with Ca++ or PTH . PTH correlated negatively not only with Ca++ ( r = -0.328 , P < 0.05 ) but also with ICTP ( r = -0.306 , P < 0.05 ) . Mean PICP was normal but ICTP was elevated and tended to correlate positively with Ca++ ( r = 0.268 , P = 0.06 ) . Vitamin D supplementation did not change PICP or ICTP considerably , despite slightly increased 1,25-(OH)2D and slightly decreased PTH . Ca++ values were normal and remained stable . In conclusion , Ca++ and PTH are poor indicators of vitamin D status in chronically immobilized elderly subjects . Furthermore , the results suggest that the increased bone resorption is not due to ' type II ' secondary hyperparathyroidism ; rather the resorption is primarily increased . Correction of vitamin D deficiency does not seem to benefit ageing bones unless adequate mechanical loading is provided BACKGROUND calcium and vitamin D deficiency are common in elderly people and lead to increased bone loss , with an enhanced risk of osteoporotic fractures . Although hip fractures are a serious consequence , few therapeutic measures are given for primary or secondary prevention . A combination of calcium and vitamin D may not be the most effective treatment for all patients . OBJECTIVE to investigate the effects of hypovitaminosis D on the calcium-parathyroid hormone endocrine axis , bone mineral density and fracture type , and the optimal role of combination calcium and vitamin D therapy after hip fracture in elderly patients . DESIGN a population -based , prospect i ve cohort study . METHODS 150 elderly subjects were recruited from the fast-track orthogeriatric rehabilitation ward within 7 days of surgery for hip fracture . This ward accepts people who live at home and are independent in activities of daily living . All subjects had a baseline medical examination , biochemical tests ( parathyroid hormone ,  25-hydroxyvitamin D  and  1,25-dihydroxyvitamin D ) and were referred for bone densitometry . RESULTS at 68 % , the prevalence of hypovitaminosis D ( 25-hydroxyvitamin D<30 nmol/l ) was high . However , only half the patients had evidence of secondary hyperparathyroidism , the rest having a low to normal level of parathyroid hormone ( ' functional hypoparathyroidism ' ) . Patients with secondary hyperparathyroidism and hypovitaminosis D had a higher mean corrected calcium , higher 1,25-dihydroxyvitamin D , lower hip bone mineral density and an excess of extracapsular over intracapsular fractures than the ' functional hypoparathyroid ' group ( P<0.01 ) . CONCLUSION there is a high prevalence of hypovitaminosis D in active , elderly people living at home who present with a hip fracture . However , secondary hyperparathyroidism occurs in only half of these patients . This subgroup attempts to maintain calcium homeostasis but does so at the expense of increased bone turnover , leading to amplified hip bone loss and an excess of extracapsular over intracapsular fractures .  Combination calcium and vitamin D treatment may be effective in preventing a second hip fracture in these patients , but its role in patients with hypovitaminosis D without secondary hyperparathyroidism and ' vitamin D-replete ' subjects needs further evaluation Summary Vitamin D is widely used in osteoporosis treatment , although the optimal dose is not known . This 1-year clinical study among 297 women aged 50–80 years old showed that a vitamin D3 dose of 6,500 IU/day was not better than the st and ard dose of 800 IU/day in improving bone mineral density ( BMD ) in the hip and spine . Introduction The purpose of this study was to determine whether a high dose of vitamin D3 was better than the st and ard dose in improving BMD and reducing bone turnover in postmenopausal women with reduced bone mass . Methods The study was a 1-year r and omized double-blind controlled trial comparing high-dose vitamin D3 with the st and ard dose .  Postmenopausal women ( n = 297 ) with a BMD T-score ≤ −2.0 in either lumbar spine ( L2–4 ) or total hip were included and r and omized to 6,500 IU vitamin D3/day ( 20,000 IU twice per week + 800 IU/day ) or 800 IU vitamin D3/day ( placebo twice per week + 800 IU/day ) . Both groups were given 1,000 mg elemental calcium/day . The primary endpoint was a change in BMD in total hip and lumbar spine ( L2–4 ) . Results After 1 year , serum 25-hydroxyvitamin D ( 25(OH)D ) increased [ mean ( SD ) ] from 71 ( 23 ) to 185 ( 34 ) nmol/l and from 71 ( 22 ) to 89 ( 17 ) nmol/l in the high- and st and ard-dose vitamin D groups , respectively . BMD at all measurement sites was unchanged or slightly improved with no significant differences between the groups . Although bone turnover was reduced in both groups , the more pronounced reduction in serum levels of the bone formation marker P1NP in the st and ard-dose group may indicate that this treatment was more efficient . Adverse events did not differ between the groups . Conclusions One year treatment with 6,500 IU vitamin D3/day was not better than 800 IU/day regarding BMD in vitamin D-replete postmenopausal women with reduced bone mass and was less efficient in reducing bone turnover CONTEXT Bariatric surgery is common and may be associated with deleterious effects on the skeleton . OBJECTIVE Our objective was to assess bone metabolism and bone mineral density ( BMD )  after Roux-en-Y gastric bypass .  DESIGN AND SETTING We conducted a 1-yr prospect i ve longitudinal study at a university hospital bariatric surgery practice and metabolic bone disease unit . PARTICIPANTS Participants included 23 obese ( mean body mass index 47 kg/m(2 ) ) men and women , aged 20 - 64 yr . MAIN OUTCOME MEASURES Serum PTH , 25-hydroxyvitamin D , osteocalcin , and urinary N-telopeptide , and BMD were assessed . RESULTS Patients lost 45 + /- 2 kg 1 yr postoperatively ( P < 0.01 ) . PTH increased early ( 3 months , 43 - 50 pg/ml ; P < 0.001 ) and urinary calcium dropped ( 161 - 92 mg/24 h ; P < 0.01 ) , despite doubling of calcium intake ( 1318 - 2488 mg/d ; P < 0.001 ) . Serum 25-hydroxyvitamin D concentrations were unchanged ( 23 - 26 ng/ml ) , although vitamin D intake increased by 260 % ( 658 IU/d at baseline to 1698 IU/d at 12 months ; P < 0.05 ) . Markers of bone remodeling rose ( P < 0.01 for both urinary N-telopeptide and osteocalcin ) , whereas BMD decreased at the femoral neck ( 9.2 % , P < 0.005 ) and at the total hip ( 8.0 % , P < 0.005 ) . These declines were strongly associated with the extent of weight loss ( femoral neck : r = 0.90 , P < 0.0001 ; and total hip : r = 0.65 , P = 0.02 ) . Lumbar spine and distal radius sites did not change . CONCLUSIONS After Roux-en-Y gastric bypass , there was evidence of calcium and vitamin D malabsorption . Bone turnover increased , and hip bone density rapidly declined . The decline in hip BMD was strongly associated with weight loss itself . Vigilance for nutritional deficiencies and bone loss in patients both before and after bariatric surgery  is crucial Objective : To study the effects of a special nutritional supplement on bone mineral density and bone turnover markers in Chilean elderly subjects with femoral osteoporosis . Setting : Public primary health care clinics in Chile . Subjects : Free living elderly subjects with femoral osteoporosis . Interventions : Subjects were r and omized to receive the usual nutritional supplement provided by the Chilean Ministry of Health or a special nutritional supplement providing , among other nutrients , 90 mg isoflavones , 800 mg calcium , 400 IU vitamin D , 60 ug vitamin K and 31 g proteins per day . Measures of Outcome : At baseline , and after six and twelve months of supplementation , body composition , bone mineral density , serum 25 OH vitamin D , intact parathyroid hormone ( iPTH ) , osteocalcin , decarboxylated osteocalcin , urinary aminoterminal telopeptide of type I collagen ( NTX ) , deoxypyridoline cross links ( Dpd ) and equol were measured . Every month , urinary daidzein was measured in a morning urine sample . Results : No differences between treatment groups were observed in body composition or bone mineral density changes . The group receiving the special supplement had a significant increase in serum 25 OH vitamin D and a significant decrease in serum iPTH and decarboxylated osteocalcin . No association between daidzein or equol excretion and changes in bone mineralization was observed . Conclusions : A special supplement delivered to elderly subjects with osteoporosis improved serum vitamin D and reduced serum iPTH and undercarboxylated osteocalcin levels but did not affect BMD Bone mobilization , lowering of bone mineral density ( BMD ) , and osteoporotic fractures are recognized in postmenopausal women with weight loss . Because a high-calcium intake suppresses bone loss in peri- and postmenopausal women , the present r and omized , double-blind , placebo-controlled study was design ed to test the hypothesis that calcium supplementation prevents net bone mobilization and consequent bone mineral loss during voluntary weight reduction in obese postmenopausal women . Subjects were placed on a moderate energy-restricted diet and either calcium supplementation ( 1 g/day ) or placebo for 6 months . Body weight , bone turnover markers ( pyridinium cross-links ) , osteocalcin , and parathyroid hormone ( PTH ) were measured at treatment weeks 1 - 5 , 7 , 10 , 13 , 16 , 20 , and 25 . Total body BMD , insulin-like growth factor , 25-hydroxyvitamin D , and sex hormone binding globulin ( SHBG ) were measured at baseline and week 25 . The calcium supplemented ( n = 15 ; age 60.9 + /- 9.4 years , body mass index [ BMI ] 33.2 + /- 4.6 kg/m2 ) and placebo ( n = 16 ; age 55.8 + /- 8.3 years , BMI 32.9 + /- 4.5 kg/m2 ) groups lost similar amounts of weight over the study interval ( 10.2 + /- 5.3 % vs. 10.0 + /- 5.2 % ) and both groups increased SHBG ( p < 0.001 ) . There was a statistical effect of calcium supplementation during weight loss to suppress pyridinium cross-links , osteocalcin , and PTH ( p < 0.05 , < 0.01 , and < 0.05 , respectively ) . Loss of BMD tended to be greater in the placebo group by 1.4 % ( p < 0.08 ) after weight loss . One gram per day calcium supplementation normalizes the increased calcium-PTH axis activity and the elevated bone turnover rate observed during moderate voluntary energy restriction in postmenopausal women Children 's vitamin D intake and status can be optimised to meet recommendations . We investigated if nutritionally balanced school meals with weekly fish servings affected serum 25-hydroxyvitamin D ( 25(OH)D ) and markers related to bone in 8- to 11-year-old Danish children . We conducted an explorative secondary outcome analysis on data from 784 children from the OPUS School Meal Study , a cluster-r and omised cross-over trial where children received school meals for 3 months and habitual lunch for 3 months . At baseline , and at the end of each dietary period , 25(OH)D , parathyroid hormone ( PTH ) , osteocalcin ( OC ) , insulin-like growth factor-1 ( IGF-1 ) , bone mineral content ( BMC ) , bone area ( BA ) , bone mineral density ( BMD ) , dietary intake and physical activity were assessed . School meals increased vitamin D intake by 0·9 ( 95 % CI 0·7 , 1·1 ) μg/d . No consistent effects were found on 25(OH)D , BMC , BA , BMD , IGF-1 or OC . However , season-modified effects were observed with 25(OH)D , i.e. children completing the school meal period in January/February had higher 25(OH)D status ( 5·5 ( 95 % CI 1·8 , 9·2 ) nmol/l ; P = 0·004 ) than children completing the control period in these months . A similar tendency was indicated in November/December ( 4·1 ( 95 % CI –0·12 , 8·3 ) nmol/l ; P = 0·057 ) . However , the effect was opposite in March/April ( –4·0 ( 95 % CI –7·0 , –0·9 ) nmol/l ; P = 0·010 ) , and no difference was found in May/June ( P = 0·214 ) . Unexpectedly , the school meals slightly increased PTH ( 0·18 ( 95 % CI 0·07 , 0·29 ) pmol/l ) compared with habitual lunch . Small increases in dietary vitamin D might hold potential to mitigate the winter nadir in Danish children 's 25(OH)D status while higher increases appear necessary to affect status throughout the year . More trials on effects of vitamin D intake from natural foods are needed
There was a suggestion that whole-body or lumbar spine BMD may be a useful biomarker in older people but not in adolescents .
This systematic review confirmed that circulating 25(OH)D is a robust and reliable marker of vitamin D status .
BACKGROUND Although serum 25-hydroxyvitamin D [ 25(OH)D ] is the currently accepted vitamin D status marker of choice , use of other biomarkers or functional endpoints have been suggested .
OBJECTIVE The objective was to systematic ally review the effectiveness of 25(OH)D , parathyroid hormone ( PTH ) , bone turnover markers , bone mineral density ( BMD ) , and calcium absorption as biomarkers of vitamin D status .