Vitamin D status and sex hormone binding globulin: determinants of bone turnover and bone mineral density in elderly women. Associations of vitamin D status with bone mineral density, bone turnover, bone loss and fracture risk in healthy postmenopausal women. The OFELY study. The Effect of Season and Vitamin D Supplementation on Bone Mineral Density in Healthy Women: A Double-Masked Crossover Study
 Vitamin D supplementation has minor effects on parathyroid hormone and bone turnover markers in vitamin D-deficient bedridden older patients. 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. 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 Physical performance and life quality in postmenopausal women supplemented with vitamin D: a two-year prospective study Serum ionized calcium, intact PTH and novel markers of bone turnover in bedridden elderly 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. 24,25 Dihydroxyvitamin D supplementation corrects hyperparathyroidism and improves skeletal abnormalities in X-linked hypophosphatemic rickets--a clinical research center study. Relationship between the effect of eldecalcitol and serum 25(OH)D level Increased Bone Resorption in the Proximal Femur in Patients with Hemiplegia Does 24R,25(OH)2-vitamin D3 prevent postmenopausal bone loss? Increased PTH and 1.25(OH)(2)D levels associated with increased markers of bone turnover following bariatric surgery. Reproducibility of serum 25-hydroxyvitamin d and vitamin D-binding protein levels over time in a prospective cohort study of black and white adults. Serum 25-Hydroxyvitamin D Concentrations and Risk for Hip Fractures 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
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 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 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 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 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 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 Aim : To investigate the effects of calcium and vitamin D supplementation on bone turnover marker levels , muscle strength and quality of life in postmenopausal Chinese women . Methods : A total of 485 healthy postmenopausal Chinese women ( 63.44±5.04 years ) were enrolled in this open-label , 2-year , prospect i ve , community-based trial . The participants were divided into group A , B , C , which were treated with calcium ( 600 mg/d ) alone , calcium ( 600 mg/d ) and cholecalciferol ( 800 IU/d ) or calcium ( 600 mg/d ) and calcitriol ( 0.25 μg/d ) , respectively , for 2 years . Serum levels of 25-hydroxyvitamin D , parathyroid hormone , β-CTX and P1NP were measured , and the muscle strength and quality of life were assessed at baseline and at 12- and 24-month follow-ups . Results : Four hundred and sixty one participants completed this study . Serum levels of 25-hydroxyvitamin D were significantly increased in group C , but not changed in groups A and B at 24-month follow-up . Serum levels of parathyroid hormone , bone turnover marker β-CTX and bone formation marker P1NP were significantly decreased in group C , while serum levels of β-CTX were increased in group A at 24-month follow-up . The participants in group C maintained the grip strength , while those in groups A and B exhibited decreased grip strength at 24-month follow-up . The quality of life for the participants in groups B and C remained consistent , but that in group A was deteriorated at 24-month follow-up . Conclusion : Supplementation with calcitriol and calcium modifies the bone turnover marker levels , and maintains muscle strength and quality of life in postmenopausal Chinese women , whereas supplementation with cholecalciferol and calcium prevents aging-mediated deterioration in quality of life 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 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 Therapy for X-linked hypophosphatemia ( XLH ) only partially corrects skeletal lesions and is often complicated by hyperparathyroidism . 24,25(OH)2 D3 improves skeletal lesions in a murine model of XLH and suppresses PTH secretion in animals . Therefore , we undertook a placebo-controlled trial of 24,25(OH)2 D3 supplementation to st and ard treatment in patients with XLH to improve bone disease and reduce hyperparathyroid complications .  Fifteen subjects with XLH receiving st and ard treatment [ 1,25(OH)2 D3 or dihydrotachysterol plus phosphate ] were evaluated , supplemented with placebo  , and reevaluated one yr later . 24,25(OH)2 D3 supplementation was then begun and studies repeated after another year . Each patient underwent a detailed evaluation of calcium homeostasis over a 24-h period . Rachitic abnormalities were assessed radiographically in children . Adults underwent bone biopsies . 24,25(OH)2 D3 normalized PTH values in nine subjects ( peak PTH was 46.5 + /- 6.6 pmol/L at entry , 42.3 + /- 5.9 pmol/L after placebo , and 23.3 + /- 5.4 pmol/L after 24,25(OH)2 D3 ) . Nephrogenous cAMP decreased at night , coincident with the decrease in PTH , and serum phosphorus was slightly greater with 24,25(OH)2 D3 . Radiographic features of rickets improved during 24,25(OH)2 D3 supplementation in children , and osteoid surface decreased in adults . 24,25(OH)2 D3 is a useful adjunct to st and ard therapy in XLH by effecting correction of hyperparathyroidism and improvement of rickets and osteomalacia In previous studies , we demonstrated that 12-month treatment with 0.75μg/day eldecalcitol increased bone mineral density in osteoporotic patients regardless of serum 25-hydroxyvitamin D ( 25(OH)D ) level , and in a 3-year r and omized double-blind clinical trial , eldecalcitol significantly reduced the incidences of vertebral and wrist fractures compared to alfacalcidol . However , it remains unclear whether the fracture risk reduction by eldecalcitol is affected by serum 25(OH)D. In the fracture prevention trial , patients with low 25(OH)D level at baseline were supplemented with 400IU/day native vitamin D3 . In the current study , patients from that trial were divided according to the tertiles of serum 25(OH)D level at 6 months after treatment initiation . The increases in lumbar and hip BMD by eldecalcitol were significantly higher in all tertiles than those by alfacalcidol .  The incidences of vertebral and osteoporotic fractures tended to be lower in each tertile of the eldecalcitol-treated group than in the corresponding tertile of the alfacalcidol-treated group , with the exception of vertebral fractures in the low tertile . We also investigated whether eldecalcitol treatment affected levels of serum 25(OH)D , serum 1,25(OH)2D , and parathyroid hormone in patients without vitamin D supplementation .  With eldecalcitol treatment , serum 1,25(OH)2D concentration was reduced by approximately 50 % , whereas serum levels of parathyroid hormone and 25(OH)D were not affected . The major findings of the present study were that eldecalcitol did not affect serum 25(OH)D levels , and that it reduced the incidence of osteoporotic fractures and increased BMD in comparison with alfacalcidol regardless of serum 25(OH)D level within the range of serum 25(OH)D concentrations at or higher than 20ng/mL. Whether eldecalcitol is similarly effective at vitamin D deficient serum 25(OH)D levels remains to be clarified . This article is part of a Special Issue entitled ' Vitamin D Workshop ' 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 Summary The effect of oral 24R,25(OH)2-vitamin D3 as a prophylactic for postmenopausal bone loss was examined . Fifty-eight healthy , early postmeno-pausal women entered a double blind therapeutic trial for 2 years . After an initial examination the women were r and omized to treatment with 10 μg 24R,25(OH)2D3 daily or placebo . Participants were thereafter examined every 3 months ( nine examinations in all ) . In both groups the forearm bone mineral ( measured by single photon absorptiometry ) , the lumbar spine mineral , and the total body mineral ( measured by dual photon absorptiometry ) fell significantly and the same magnitude . Further-more , serum calcium , serum alkaline phosphatase concentration , and fasting urinary hydroxyproline were unchanged , as were the 24-hour urinary calcium excretion and the intestinal radiocalcium absorption . Our findings demonstrate that 24R,25(OH)2D3 treatment has no prophylactic effect on postmenopausal bone loss and does not alter calcium metabolic variables 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 Prospect i ve epidemiologic studies generally rely on 1 baseline biologic sample from participants for measurement of prediagnostic biomarkers , assuming that 1 measurement adequately represents the participant 's " typical " level . The body of work assessing the reproducibility of circulating serum 25-hydroxyvitamin D ( 25(OH)D ) levels over time focuses almost exclusively on population s of European descent , and data for vitamin D-binding protein ( VDBP ) are virtually nonexistent . Thus , the authors measured levels of serum 25(OH)D and VDBP twice in sample s collected between 2005 and 2008 from 225 participants ( 155 black , 70 white ) in the Southern Community Cohort Study .  Reproducibility for 25(OH)D was uniformly high , with adjusted intraclass correlation coefficients ( ICCs ) of 0.84 ( 95 % confidence interval ( CI ) : 0.79 , 0.88 ) for blacks and 0.92 ( 95 % CI : 0.87 , 0.95 ) for whites , and there was substantial agreement for assignment of 25(OH)D quartile ( κ = 0.83 , 95 % CI : 0.78 , 0.87 ) and vitamin D adequacy status ( κ = 0.76 , 95 % CI : 0.69 , 0.83 ) . VDBP levels were highly stable over time , with adjusted ICCs of 0.97 ( 95 % CI : 0.96 , 0.98 ) for blacks and 0.96 ( 95 % CI : 0.93 , 0.97 ) for whites . These findings suggest that single , baseline 25(OH)D and VDBP serum measurements provide reasonably representative measures of these compounds for both white and black adults , demonstrating their utility as epidemiologic biomarkers in prospect i ve studies Context Vitamin D supplementation may help prevent fractures , but the relationship between blood vitamin D concentrations and fracture risk is unclear . Contribution These authors observed an increased risk for hip fracture among women with lower serum 25-hydroxyvitamin D [ 25(OH ) vitamin D ] concentrations that was independent of measures of frailty , body mass index , physical function , and falls . Caution The authors did not measure bone mineral density ( BMD ) , so they could not determine whether 25(OH ) vitamin D concentrations give different information about fracture risk than that offered by BMD . Implication Low serum 25(OH ) vitamin D concentrations seem to be associated with a higher hip fracture risk . The Editors Vitamin  D deficiency is common in older adults , especially during the winter ( 1 ) and in homebound population s ( 2 ) , general medical in patients ( 3 ) , and community-dwelling women admitted to the hospital with acute hip fracture ( 4 ) . A recently published evidence -based report on vitamin D and bone health ( 5 ) found the level of evidence for an association between serum 25-hydroxyvitamin D [ 25(OH ) vitamin D ] concentrations and fracture risk to be inconsistent ( 5 ) . Since publication of that review , 1 prospect i ve study ( 6 ) reported no relationship between serum 25(OH ) vitamin D concentrations and fractures , whereas another ( 7 ) reported a significantly lower risk for hip fracture with 25(OH ) vitamin D concentrations greater than 60 nmol/L. Vitamin D concentration could be associated with fractures in several ways . It could influence muscle strength and balance , both of which contribute to falls and disability ( 810 ) . The association between 25(OH ) vitamin D concentrations and fracture may also be influenced by renal function , because renal insufficiency has been linked to fracture ( 11 ) and to vitamin D deficiency ( 12 ) . Several interactions between vitamin D and estrogen receptors have been described ( 13 ) ; hormone therapy has been shown to reverse abnormalities in vitamin D metabolism ( 14 ) , and low vitamin D concentrations have also been linked to higher bone turnover ( 15 , 16 ) . Thus , sex-steroid hormones and bone turnover could contribute to the association between 25(OH ) vitamin D concentration and fractures . We conducted a nested casecontrol study within the WHI-OS ( Women 's Health Initiative Observational Study ) among 400 case- patients with adjudicated incident hip fracture and 400 control participants . We tested whether low serum 25(OH ) vitamin D concentrations are associated with a higher risk for hip fractures in community-dwelling women and whether this relationship may be mediated by poor physical functioning , frailty , falls , sex-steroid hormones , renal function , or bone turnover . Methods Study Population Our study population came from the WHI-OS , a prospect i ve cohort study that enrolled 93676 women between 1994 and 1998 at 40 U.S. clinical centers ( age range , 50 to 79 years ) . Study methods are described in detail elsewhere ( 17 ) . In brief , women were eligible if they were postmenopausal , were unlikely to move or die within 3 years , were not enrolled in the WHI clinical trials , and were not currently participating in any other clinical trial . The human subjects review committees from each participating institution approved the study . Follow-up and Outcome Ascertainment We sent women question naires annually to report any hospitalization and other outcomes , including fractures . As of August 2004 , median follow-up duration was 7.1 years ( range , 0.7 to 9.3 years ) . At that time , 3.7 % of participants had withdrawn or were lost to follow-up and 5.3 % had died . We review ed medical records to verify cases of hip fracture , and blinded central adjudicators confirmed the cases ( 18 ) . We excluded patients with pathologic hip fractures . Nested CaseControl Study Design The present study is a casecontrol study nested within the prospect i ve design of WHI-OS . We excluded women who had a history of hip fracture ; were receiving hormone therapy up to 1 year before enrollment ; or were currently receiving and rogens , selective estrogen receptor modulators , antiestrogens , or other osteoporosis treatments ( bisphosphonates , calcitonin , or parathyroid hormone ) . We also excluded women with insufficient serum stored or of unknown ethnicity , leaving 39793 eligible participants . Of these , 404 women had a hip fracture . We r and omly selected 400 of these women to form the incident hip fracture group . For each case-patient , we selected 1 control participant who was within 1 year of the case-patient 's age at screening , was of matching race or ethnicity , and had their blood drawn within 120 days of the case-patient 's blood draw date ; 99 % of case- patients and control participants were matched within 30 days . Baseline Clinical Variables We divided clinical centers into 3 geographic regions on the basis of latitude : northern ( > 40 N ) , middle ( 35 to 40 N ) , and southern ( < 35 N ) . We ascertained all covariates at baseline . Clinic interviewers recorded current use of prescription medications by direct inspection of medicine containers . We entered prescription names into the WHI data base and assigned drug codes by using Medispan software ( First Data Bank , San Bruno , California ) . Average amounts of elemental calcium and vitamin D preparations were entered directly from supplement containers . Dietary intakes of calcium and vitamin D were assessed by using a semiquantitative food-frequency question naire ( 19 ) . Total calcium and vitamin D intake was defined as the sum of diet and supplements . We used question naires to ascertain date of birth , race or ethnicity , age at menopause , history of any fracture after age 55 years , smoking , parental history of hip fracture , self-rated health status , and alcohol consumption . We classfied physical activity on the basis of frequency and duration of walking and mild , moderate , and strenuous activities in the previous week . We calculated kilocalories of energy expended in 1 week as the metabolic equivalent ( kcal hours/week per kg ) ( 20 ) . We measured physical function by using the R AND Short Form-36 physical function scale , which comprises 10 items measuring whether health now limits physical function in moderate or vigorous activity ( 2 items ) ; strength to lift , carry , stoop , bend , or stair climb ( 4 items ) ; ability to walk various distances without difficulty ( 3 items ) ; and self-care ( 1 item ) ( 21 ) . The scale is scored from 0 to 100 , with higher scores indicating better physical function . We compared women with a score greater than 90 versus those with a score less than or equal to 90 , a cutoff value corresponding to the median score . We computed a frailty score , which included self-reported muscle weakness and impaired walking speed ( R AND Short Form-36 physical function scale score < 75 ) , exhaustion ( R AND Short Form-36 vitality scale score < 55 ) , low physical activity ( lowest quartile of physical activity ) , and unintended weight loss between baseline and 3 years of follow-up ( 22 ) . A woman was considered frail if she reported 3 or more of these indicators . Weight was measured on a balance-beam scale with the participant dressed in indoor clothing without shoes . Height was measured by using a wall-mounted stadiometer . Body mass index was calculated as weight ( in kg ) divided by height ( in m2 ) . Laboratory Procedures Laboratory personnel blinded to casecontrol status obtained a 12-hour fasting blood sample at the baseline visit , which was processed and stored at 80C according to strict quality control procedures ( 23 ) . Serum 25(OH ) vitamin D concentrations and sex-steroid hormone levels were measured at the Reproductive Endocrine Research Laboratory at the University of Southern California .  25-Hydroxyvitamin vitamin D was measured by using a radioimmunoassay with DiaSorin reagents ( DiaSorin , Stillwater , Minnesota ) . The sensitivity of the assay was 3.75 nmol/L. The interassay coefficients of variation were 11.7 % , 10.5 % , 8.6 % , and 12.5 % at 14.0 , 56.8 , 82.5 , and 122.5 nmol/L , respectively . Estradiol and testosterone concentrations were quantified by using sensitive and specific radioimmunoassays after organic solvent extraction and celite column partition chromatography ( 2427 ) . The intra- and interassay coefficients of variation were 7.9 % and 8 % to 12 % , respectively , for estradiol and 6 % and 10 % to 12 % , respectively , for testosterone . We calculated bioavailable hormone concentrations by using mass action equations ( 2830 ) . We measured sex hormonebinding globulin by using a solid-phase , 2-site chemiluminescent immunoassay . The intra- and interassay coefficients of variation were 4.1 % to 7.7 % and 5.8 % to 13 % , respectively . Serum cystatin C , a marker of renal function that is independent of age and weight , was measured at Medical Research Laboratories International , Highl and Heights , Kentucky , by using the Dade Behring BN-II nephelometer and Dade Behring reagents ( Dade Behring , Ramsey , Minnesota ) in a particle-enhanced immunonepholometric assay . Serum C-terminal telopeptide of type I collagen and aminoterminal procollagen extensions propeptide were measured by immunoassay ( Synarc , Lyon , France ) . Statistical Analysis We used chi-square and t tests to compare baseline characteristics between case- patients with hip fracture and matched control participants . We assigned 25(OH ) vitamin D concentrations to quartile categories defined on the basis of the distribution in the control participants . To further assess confounding , we compared baseline characteristics across quartiles of 25(OH ) vitamin D concentrations in case- patients and control participants combined . We calculated the P values for trend by using logistic regression and coding the variable of interest as a continuous variable . We assessed the association between serum 25(OH ) vitamin D concentrations and incident hip fracture in conditional logistic regression models that retained the matched casecontrol design . We first examined the unadjusted associations and then adjusted for age , 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
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 .