Comparison of the effects of calcium loading with calcium citrate or calcium carbonate on bone turnover in postmenopausal women

Calcium supplementation is known to increase bone mineral density and decrease fractures, but the relative efficacy of different forms of calcium supplementation is not established. We compared the effects of calcium carbonate and calcium citrate on markers of bone resorption in older postmenopausal women in an open-labeled crossover study. Forty women were randomized to receive 1000 mg/day of either calcium citrate or calcium carbonate for 12 weeks, followed by a 2-week washout without calcium supplements and 12 weeks treatment with the alternate calcium supplement. All women received vitamin D (900 IU/day). Thirty-four women (25 Caucasian, nine Hispanic) completed the study. No significant differences in the decrease in parathyroid hormone (PTH) or bone specific alkaline phosphatase or the increase in urinary calcium/creatinine were detected between the two treatments. However, calcium citrate supplementation decreased the collagen cross-link resorption markers, urinary N-telopeptide (–30%), C-telopeptide (–31%), free deoxypyridinoline (19%) and serum N-telopeptide (–8%), compared to no significant change following calcium carbonate supplementation (+2%, +3%, +2% and +2%, respectively; P<0.05). Calcium citrate decreased markers of bone resorption significantly more than calcium carbonate in postmenopausal women, although no differences in their effects in calcium excretion or PTH were detected.     

Acute Effects of Calcitonin Nasal Spray on Serum C-telopeptide of Type 1 Collagen (CTx) Levels in Elderly Osteopenic Women with Increased Bone Turnover

Salmon calcitonin is a potent inhibitor of osteoclastic activity. The effect of calcitonin in elderly women with high bone turnover at higher risk of developing osteoporosis has not been studied. To investigate acute effects of calcitonin treatment on bone resorption markers in elderly women, we conducted a randomized trial in women >65 years of age with high bone turnover assessed as urinary N-telopeptide of type-I collagen (NTx) levels 1 SD higher than mean premenopausal levels, which was irrespective of bone density. A total of 98 elderly women were randomly assigned to receive either 200 IU calcitonin nasal spray (n = 75) with calcium (500 mg) and vitamin D (200 IU) or calcium and vitamin D (n = 23) alone for 6 months. Blood and urine samples were collected at 0, 2, 4, and 6 months and analyzed for urinary NTx and serum C-telopeptide of type-1 collagen (CTx). At baseline, mean age was 72.1 ± 4.7 (mean ± SD) in the calcitonin group and 72.2 ± 6 years in the control group. The spine and total hip BMD, serum PTH levels and urinary calcium/creatinine ratios were similar in both groups. Mean BMD was in the osteopenic range in both groups. Calcitonin treatment resulted in significant decreases in serum CTx levels, 2, 4 and 6 months after treatment as compared to baseline, and after 4 and 6 months as compared to controls. A maximum decrease from baseline of 33% was seen at 6 months. The urinary resorption marker, urine NTx, showed a significant decrease in the calcitonin group when compared to baseline only at the 6-month time point. Analysis of least significance change (LSC) showed that 70% of calcitonin patients were categorized as responders using serum CTx after 6 months of treatment. We conclude that 200 IU calcitonin effectively decreases bone resorption within 60 days of therapy, thus preventing further bone loss in elderly women who are at a high risk of developing osteoporosis.     

Effects of a short-term vitamin D and calcium supplementation on body sway and secondary hyperparathyroidism in elderly women.

Long-term vitamin D and calcium supplementation is effective in reducing nonvertebral fractures in elderly people. Increased bone fragility caused by secondary hyperparathyroidism (sHPT) and impaired balance are known risk factors for hip fractures. The hypothesis is that short-term therapy with calcium and vitamin D may improve body sway as well as sHPT more effectively than calcium monotherapy. The effects of 8 weeks of supplementation with vitamin D (cholecalciferol) and calcium on body sway and biochemical measures of bone metabolism were measured. The sample consisted of 148 women (mean [+/-SD] age, 74 +/- 1 years) with a 25-hydroxycholecalciferol level below 50 nmol/liter. They received either 1200 mg of calcium plus 800 IU of vitamin D or 1200 mg of calcium per day. We measured intact parathyroid hormone (PTH), markers of bone turnover, and body sway before and after treatment. Falls and fractures among the participants were followed over a 1-year period. Compared with calcium mono, supplementation with vitamin D and calcium resulted in an increase in serum 25-hydroxyvitamin D of 72% (p < 0.0001), a decrease in the serum PTH of 18% ( p = 0.0432), and a decrease in body sway of 9% (p = 0.0435). The mean number of falls per subject during a 1-year follow-up period was 0.45 for the calcium mono group and 0.24 for the calcium and vitamin D group (p = 0.0346). Short-term supplementation with vitamin D and calcium improves sHPT and body sway and therefore may prevent falls and subsequent nonvertebral fractures in elderly women.     

Calcium Metabolism in Pre- and Postmenopausal Morbidly Obese Women at Baseline and After Laparoscopic Roux-En-Y Gastric Bypass

Background: The authors evaluated calcium metabolism in obese women, before and after menopause, at baseline and at 6 and 12 months after laparoscopic Roux-en-Y gastric bypass (LRYGBP). LRYGBP restricts food intake and produces physiological changes that may be similar to those after high Billroth II subtotal gastrectomy. Methods: Serum calcium (Ca), phosphate, bone-specific alkaline phosphatase (BSAP) and 25-hydroxyvitamin D3 (25-OH D) were measured at baseline and 12 months after LRYGBP. Urinary N-telopeptide (u-NTX) was measured at baseline and serum C-telopeptide (s-CTX) at 6 and 12 months after LRYGBP. Parathormone (PTH) was measured at baseline and 6 and 12 months after LRYGBP. Patients were divided into 2 groups: Group I (n=30) pre-menopausal women aged 18-42 y, and Group II (n=30) post-menopausal women aged 40-71 y. Patients with renal, hepatic, metabolic and bone disease, smoking women, as well as patients with u-NTX values at baseline >67 nMBCE/mMCr were excluded. Results: At baseline, PTH was elevated in 10% of patients in each group, correlated positively with BMI, and low serum calcium values were found in 30% of Group I and 16.7% of Group II. High values of serum C-telopetide were seen in Group I at 6 months after surgery and in Group II 12 months after LRYGBP. Group II showed a greater increase in BSAP at 12 months after LRYGBP. 25-0H D decreased in both groups, and a progressive increase in PTH was observed. Serum calcium did not change in both groups. Conclusion: Calcium metabolism is altered in pre- and post-menopausal women following LRYGBP. Calcium and vitamin D supplementation is strongly advised in all patients.     

Consumption of a high calcium mineral water lowers biochemical indices of bone remodeling in postmenopausal women with low calcium intake

Many postmenopausal women have a calcium intake far below the recommended amount and, in addition to attempting to improve their diet, need a calcium supplement. The aim of the study was to assess the effects of the consumption of a high calcium mineral water (HCaMW) on biochemical indices of bone remodeling in postmenopausal women with low Ca intake. A 6-month randomized double-blind placebo-controlled trial was designed to assess the effects of a daily consumption of 1 liter of a HCaMW (596 mg Ca/l) on serum parathyroid hormone (PTH) and biochemical markers of bone remodeling in postmenopausal women with a dietary Ca intake lower than 700 mg/day. The placebo group drank 1 liter of a mineral water with a low calcium content (10 mg/l). One hundred eighty healthy women were recruited (mean age: 70.1±4.0 years); 152 completed the 6-month trial. The changes from baseline of biochemical indices after 6 months consisted of a significant 14.1% decrease of serum PTH, osteocalcin (–8.6%), bone alkaline phosphatase (–11.5%), serum (–16.3%) and urine (–13.0%) type-1 collagen C-telopeptide in the HCaMW group compared to the placebo group, where all biochemical indices increased after 6 months. The additive effect of a small vitamin D supplement (400 iu/day) was also evaluated. In women receiving vitamin D in addition to HCaMW, the decrease in bone indices was not found to be greater than in women drinking only the HCaMW. A daily supplement of 596 mg of Ca through the consumption of 1 l of HCaMW was able to lower serum PTH and the indices of bone turnover in postmenopausal women with a low Ca intake. This could contribute to the repair of calcium deficiency and to the reduction of age-related bone loss in this population.This study was supported by a grant from Evian.     

Biochemical Responses of Bone Metabolism to 1,25-Dihydroxyvitamin D Administration in Black and White Women

The basis for the racial difference in bone mass between black and white women is not known. Lower bone turnover, better renal calcium conservation, and decreased sensitivity to parathyroid hormone (PTH) have been proposed as explanations. A dynamic comparison of osteoblast function, utilizing stimulation by 1,25-dihydroxyvitamin D [1,25(OH)₂D], has not been tested between these two ethnic groups. We compared well-matched black (n= 15) and white (n= 15) premenopausal women, before and during 5 days of 1,25(OH)₂D administration (1.0 μg/day) in order to assess dynamic indices of bone metabolism. As expected, at baseline, black women had lower levels of serum 25-hydroxyvitamin D and biochemical markers of bone turnover with slightly higher levels of PTH. Black women also had superior renal calcium conservation than white women at baseline. In response to 1,25(OH)₂D administration, black women had a slightly greater increase in serum calcium and greater decrement in PTH. Moreover, black women showed a lesser increment in urinary calcium than white women and a more robust increase in two markers of bone formation – osteocalcin and carboxyterminal propeptide of type 1 procollagen – than white women. There were no changes in bone resorption indices in either race upon 1,25(OH)₂D administration. These data provide preliminary evidence that black women conserve calcium more efficiently under both static and dynamic conditions, and also appear to have better osteoblastic functional reserve than white women. Received: 22 June 1999 / Accepted: 6 September 1999     

Longitudinal Evaluation of Vitamin D Status in Healthy Subjects from Southern Italy: Seasonal and Gender Differences

Vitamin D status is currently considered among the relevant determinants of skeletal integrity. Since vitamin D levels present seasonal variations, we longitudinally studied young healthy men and women in order to investigate the related physiologic modifications of both calcium homeostasis and bone remodeling. Thirty-two men (mean age 39.4 ± 7.8 years) and 58 premenopausal women (aged 36.9 ± 6.4 years) from southern Italy were studied. In all subjects the following parameters were measured both in winter and in summer: serum calcium, phosphorus, creatinine, total alkaline phosphatase activity, 25-hydroxyvitamin D (25OHD), parathyroid hormone (PTH), osteocalcin (BGP), together with urinary calcium (Ca/Cr), total pyridinoline (Pyr/Cr) and deoxypyridinoline (d-Pyr/Cr), corrected for creatinine excretion. In both sexes 25OHD levels were significantly higher in summer, while PTH values were lower, than in winter. The prevalence of hypovitaminosis D, defined by concentrations of 25OHD lower than 30 nmol/l, was 17.8% in winter and 2.2% in summer in the whole sample, while it was 27.8% and 3.4%, respectively, among female subjects. Indeed male subjects did not display hypovitaminosis D, having throughout the year significantly higher calcium and 25OHD levels together with lower PTH values, than the women. Moreover, alkaline phosphatase total activity was more elevated in men both in winter and in summer. In women, during winter, bone remodeling markers levels were higher while urinary calcium levels were lower than in summer. In the whole sample serum 25OHD correlated positively with serum calcium and inversely with PTH. The seasonal percentage variations in PTH were inversely correlated with those of Ca/Cr. Our results show a relatively high prevalence of subclinical vitamin D deficiency among young healthy women from southern Italy. Significant gender-specific differences have been demonstrated in both calcium homeostasis and skeletal remodeling indexes; the seasonal fluctuations in the vitamin D–PTH axis are accompanied by cyclical variations of bone turnover rate, which were more pronounced in women. Received: 11 January 2001 / Accepted: 6 July 2001     

Genetic contribution to bone metabolism, calcium excretion, and vitamin D and parathyroid hormone regulation.

A classical twin study was performed to assess the relative contribution of genetic and environmental factors to bone metabolism, calcium homeostasis, and the hormones regulating them. It was examined further whether the genetic effect is menopause dependent. The subjects were 2136 adult twins (98.3% female): 384 monozygotic (MZ) and 684 dizygotic (DZ) twin pairs. The intraclass correlations were calculated, and maximum likelihood model fitting was used to estimate genetic and environmental variance components. The intraclass correlations for all of the variables assessed were higher in MZ twin pairs. The heritabilities (95% CIs) obtained from model fitting for hormones regulating bone metabolism and calcium homeostasis were parathyroid hormone (PTH), 60% (54-65%); 25-hydroxyvitamin D [25(OH)D]; 43% (28-57%), 1,25-hydroxyvitamin D [1,25(OH)], 65% (53-74%); and vitamin D binding protein 62% (56-66%). The heritabilities (95% CIs) for markers of bone formation also were assessed; bone-specific alkaline phosphatase (BSAP), 74% (67-80%), and osteocalcin, 29% (14-44%); marker of bone resorption deoxypyridinoline (DPD), 58% (52-64%); and measure of calcium homeostasis 24 h urine calcium, creatinine (Cr), 52% (41-61%). The magnitude of genetic influence differed with menopause for most variables. This study provides evidence for the importance of genetic factors in determining bone resorption and formation, calcium excretion, and the hormones regulating these processes. It shows for the first time a clear genetic effect on bone resorption in premenopausal women and the regulation of PTH, vitamin D metabolism, and calcium excretion. The genes controlling bone hormones and markers are likely to be useful therapeutic and diagnostic targets.     

Comparative effects of vitamin K and vitamin D supplementation on prevention of osteopenia in calcium-deficient young rats

The aim of this study was to clarify the difference in the effects of vitamin K and vitamin D supplementation on the development of osteopenia in young rats under mild calcium deficiency. Sixty female Sprague-Dawley rats, 6 weeks of age, were randomized by stratified weight method into six groups with 10 rats in each group: baseline control, 0.5% (normal) calcium diet, 0.1% (low) calcium diet, 0.1% calcium diet + vitamin K (30 mg/100 g, food intake), 0.1% calcium diet + vitamin D (25 microg/100 g, food intake), and 0.1% calcium diet + K + D. After 10 weeks of feeding, serum calcium, 25-hydroxyvitamin D(3) [25 (OH) D(3)], 1,25-dihydroxyvitamin D(3) [1,25 (OH)(2) D(3)], and parathyroid hormone (PTH) levels were measured, and intestinal calcium absorption and renal calcium reabsorption were evaluated. Bone histomorphometric analyses were performed on cortical bone of the tibial shaft and cancellous bone of the proximal tibia. Calcium deficiency induced hypocalcemia, increased serum PTH and 1,25 (OH)(2) D(3) levels with decreased serum 25 (OH) D(3) level, stimulated intestinal calcium absorption and renal calcium reabsorption, and reduced maturation-related cortical bone gain as a result of decreased periosteal bone gain and enlarged marrow cavity but did not significantly influence maturation-related cancellous bone gain. Vitamin K supplementation in calcium-deficient rats stimulated renal calcium reabsorption, retarded the abnormal elevation of serum PTH level, increased maturation-related cancellous bone gain, and retarded the reduction in maturation-related cortical bone gain. On the other hand, vitamin D supplementation in calcium-deficient rats stimulated intestinal calcium absorption via increased serum 1,25 (OH)(2) D(3) level with prevention of the abnormal elevation of serum PTH level, prevented hypocalcemia, reduced the maturation-related cancellous bone gain, and prevented the reduction in periosteal bone gain and enhanced enlargement of the marrow cavity with no significant effect on the reduction in maturation-related cortical bone gain. However, no synergistic effect of vitamin K and vitamin D on intestinal calcium absorption, renal calcium reabsorption, and cancellous and cortical bone mass was found. This study shows the differential effects of vitamin K and vitamin D supplementation on the development of osteopenia in young rats under mild calcium deficiency. Vitamin K supplementation stimulates renal calcium reabsorption, increases maturation-related cancellous bone gain, and retards the reduction in maturation-related cortical bone gain, whereas vitamin D supplementation stimulates intestinal calcium absorption and prevents the reduction in maturation-related periosteal bone gain by inducing accumulation of calcium from cancellous and endocortical bone.     

Relationship between serum 25-hydroxyvitamin D and bone resorption markers in vitamin D insufficiency

It is known that nursing-home patients with vitamin D insufficiency have elevated serum parathyroid hormone (PTH) as well as raised serum alkaline phosphatase (ALP). Although it is well known that vitamin D insufficiency and secondary hyperparathyroidism are common among the elderly in western countries, there is continuing controversy over the level of serum 25-hydroxyvitamin D [25(OH)D] necessary for bone health. We approached this issue by examining the relationships between serum 25(OH)D, ionized calcium, PTH, and ALP and the urinary bone resorption markers hydroxyproline, pyridinoline, and deoxypyridinoline, corrected for creatinine (OHPr/Cr, Pyd/Cr, and Dpd/Cr, respectively), in 486 postmenopausal women of mean age 63 (SD 9.5) years, who were referred to our osteoporosis and menopause clinics for investigation. When the patients were divided into two groups with 25(OH)D above and below 20 nmol/L, 30 nmol/L, 40 nmol/L, 50 nmol/L, 60 nmol/L, or 70 nmol/L, the most significant differences between the two groups thus derived was found at a serum 25(OH)D level of 60 nmol/L (P < 0.001 for all markers). The most significant difference between groups for serum PTH was found when the patients were divided at a serum 25(OH)D of 50 nmol/L. PTH, OHPr/Cr, Pyd/Cr, and ALP were inversely related to serum 25(OH)D. PTH was inversely related to serum ionized calcium. There was a trend for ionized calcium to be positively related to 25(OH)D, but this did not reach statistical significance. We conclude that rises in three bone resorption markers and ALP can be detected in postmenopausal women when the serum 25(OH)D level falls below 60 nmol/L. Levels above this may be required for optimal bone health.     

A randomized controlled trial of vitamin D supplementation on preventing postmenopausal bone loss and modifying bone metabolism using identical twin pairs.

Vitamin D supplementation, when given with calcium, has been shown to increase bone mineral density (BMD) and reduce the incidence of hip fracture in elderly subjects. Despite its widespread use, the benefits of vitamin D supplementation in younger women and as a single agent are less clear. We performed a randomized co-twin, placebo-controlled, double-blind trial over 2 years to measure the effect of vitamin D3 supplementation on bone density and bone metabolism in young postmenopausal women. Seventy-nine monozygotic (MZ) twin pairs (mean age, 58.7 years; range, 47-70 years) were recruited. For each twin pair, one was randomized to 800 IU cholecalciferol/day for 2 years and the other was randomized to placebo. BMD was measured at the spine and hip and heel ultrasound at baseline, 12, 18, and 24 months. Samples were collected at 0, 3, and 6 months to measure serum calcium, 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), osteocalcin, and urinary deoxypyridinoline (DPD). In total, 64 pairs completed the study. No differences in baseline characteristics were seen between the groups. At 6 months, the treatment group had an increase in serum vitamin D [mean +/- SEM intrapair difference, 14.1+/-2.4 microg/liter (p < 0.001)]. There were no significant differences in other serum measurements or bone markers at 3 months or 6 months. At 24 months, no significant treatment effect was seen on BMD or calcaneal ultrasound change within pairs. Subanalysis of treatment response by vitamin D receptor (VDR) genotype revealed no significant difference in effect on BMD variables with treatment. On the basis of these results, vitamin D supplementation, on its own, cannot be recommended routinely as an osteoporosis prevention for healthy postmenopausal women with normal vitamin D levels under the age of 70 years.     

Markers of Bone and Calcium Metabolism Following Gastric Bypass and Laparoscopic Adjustable Gastric Banding

BACKGROUND: Several studies have suggested that morbid obesity is associated with vitamin D deficiency and elevated parathyroid hormone (PTH). Studies have also suggested that there is an increase in vitamin D deficiency, bone resorption, and elevated PTH after gastric bypass surgery. Few studies have evaluated markers of bone and calcium metabolism after laparoscopic adjustable gastric banding or compared these results to those after gastric bypass. METHODS: Data on all patients undergoing primary gastric bypass (GBP; n = 979) and laparoscopic adjustable gastric banding (LAGB; n = 269) procedures at a tertiary-referral center from June 1996 through March 2005 were reviewed from a prospective database. Only patients with 25OH vitamin D levels available were included in this study (n = 534; GBP = 403, LAGB = 131). All patients were advised to take at least 1,200 mg calcium and 800-1,200 IU of vitamin D daily before and subsequent to their operation. Markers for bone metabolism [25OH Vitamin D, corrected serum calcium, alkaline phosphatase (AP), and PTH] were evaluated preoperatively and 3, 6, 12, and 24 months postoperatively. An analysis of variance and chi-square were performed to determine differences between the operative groups. Linear regression analysis was performed to evaluate the relationship between preoperative body mass index (BMI) and 25OH vitamin D and PTH levels and between percent excess weight loss and 25OH vitamin D and PTH after surgery. RESULTS: Sixty-four percent of all patients presented with vitamin D deficiency (<20 ng/ml) and 14% presented with elevated PTH preoperatively. Mean 25OH vitamin D levels and AP levels increased significantly after GBP surgery (vitamin D, 17 to 25 ng/ml 12 months post-op; AP, 80 to 90 IU/L 24 months post-op). Corrected calcium levels remained within normal limits and showed no change over time after both procedures. AP levels significantly increased from 76 IU/l preoperatively to 82 IU/l 6 months after LAGB surgery and then decreased to 59 IU/l 24 months after LAGB surgery. Linear regression analysis of preoperative vitamin D, PTH, and BMI values showed a significant positive relationship between initial BMI and PTH (r = 0.29) and a significant negative relationship between vitamin D and initial BMI (r = -0.19). A significant positive linear relationship between vitamin D and percent excess weight loss was evident 12 and 24 months after GBP surgery (r = 0.39 and 0.57, respectively). A negative relationship was evident between PTH and vitamin D 6 months after GBP surgery (r = -0.35) and 12 months after LAGB surgery (r = -0.61). CONCLUSIONS: These findings suggest that morbid obesity is associated with vitamin D deficiency, and elevated PTH and with adequate supplementation, GBP, and particularly LAGB, patients can improve their bone metabolism abnormalities related to obesity. Furthermore, adequate supplementation for GBP patients may attenuate the increased risk for bone loss associated with malabsorption from the bypass.     

Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women.

Dietary supplementation with vitamin K(1), with vitamin D(3) and calcium or their combination, was examined in healthy older women during a 2-year, double-blind, placebo-controlled trial. Combined vitamin K with vitamin D plus calcium was associated with a modest but significant increase in BMC at the ultradistal radius but not at other sites in the hip or radius. INTRODUCTION: The putative beneficial role of high dietary vitamin K(1) (phylloquinone) on BMD and the possibility of interactive benefits with vitamin D were studied in a 2-year double-blind, placebo-controlled trial in healthy Scottish women > or =60 years of age. MATERIALS AND METHODS: Healthy, nonosteoporotic women (n = 244) were randomized to receive either (1) placebo, (2) 200 microg/day vitamin K(1), (3) 10 microg (400 IU) vitamin D(3) plus 1000 mg calcium/day, or (4) combined vitamins K(1) and D(3) plus calcium. Baseline and 6-month measurements included DXA bone mineral scans of the hip and wrist, markers of bone turnover, and vitamin status. Supplementation effects were tested using multivariate general linear modeling, with full adjustment for baseline and potential confounding variables. RESULTS: Significant bone mineral loss was seen only at the mid-distal radius but with no significant difference between groups. However, women who took combined vitamin K and vitamin D plus calcium showed a significant and sustained increase in both BMD and BMC at the site of the ultradistal radius. Serum status indicators responded significantly to respective supplementation with vitamins K and D. Over 2 years, serum vitamin K(1) increased by 157% (p < 0.001), the percentage of undercarboxylated osteocalcin (%GluOC) decreased by 51% (p < 0.001), serum 25-hydroxyvitamin D [25(OH)D] increased by 17% (p < 0.001), and PTH decreased by 11% (p = 0.049). CONCLUSIONS: These results provide evidence of a modest synergy in healthy older women from nutritionally relevant intakes of vitamin K(1) together with supplements of calcium plus moderate vitamin D(3) to enhance BMC at the ultradistal radius, a site consisting of principally trabecular bone. The substantial increase in gamma-carboxylation of osteocalcin by vitamin K may have long-term benefits and is potentially achievable by increased dietary intakes of vitamin K rather than by supplementation.     

Short-term calcitriol administration improves calcium homeostasis in adults with cystic fibrosis

Osteoporosis is a well-defined health risk in cystic fibrosis (CF) patients due to many factors. Vitamin D insufficiency, despite routine cholecalciferol supplementation in CF patients, may contribute to a relative secondary hyperparathyroidism and possibly deficient bone mineralization. An alternate form of vitamin D, calcitriol, was studied to determine short-term effects on fractional calcium absorption and other calciotropic markers in 10 adult CF subjects and in 10 age-, sex- and body mass index (BMI)-matched controls. Serum fractional absorption of (45)Ca was determined after a calcium-containing meal prior to calcitriol intervention. Other measurements included serum parathyroid hormone (PTH), ionized calcium, 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25(OH)(2)D) and urinary calcium:creatinine and N-telopeptide (NTx) concentrations. Both groups were then given calcitriol (0.5 micro g p.o. b.i.d. for 14 days) and restudied following the same protocol. Both groups increased their fractional absorption of (45)Ca after calcitriol ( p=0.015 CF subjects, p=0.001 controls), although calcitriol tended to be less effective in the CF group compared with the controls ( p=0.055). Post-prandial serum PTH concentrations were suppressed compared with baseline in both groups ( p=0.03 CF subjects, p=0.006 controls). Urinary NTx concentrations, a marker for bone resorption, decreased significantly in CF subjects after calcitriol (96.0+/-16.0 vs 63.9+/-12.7 nmol BCE/mmol Cr, p=0.01) and remained unchanged in the control group. The controls had an increase in serum 1,25(OH)(2)D concentrations (69.9+/-4.2 vs 90.7+/-9.6 pmol/l, p=0.02) while there was no significant change in the CF group. Oral calcitriol administration appears to improve markers of calcium balance in adults with CF by increasing fractional absorption of (45)Ca and lowering PTH concentrations, similar to its known effects in healthy subjects, while also suppressing urinary NTx, a marker of bone turnover.     

Effects of Race on Diurnal Patterns of Renal Conservation of Calcium and Bone Resorption in Premenopausal Women

Previous studies showed differences in bone and mineral metabolism in African-Americans and Caucasians: reductions in serum 25-hydroxyvitamin D [25(OH)D], urinary calcium and skeletal remodeling and moderate secondary hyperparathyroidism. Diurnal studies were carried out in 7 African-American and 7 white normal premenopausal women matched for age, weight and height to further characterize these racial differences in calcium homeostasis. Serum 25(OH)D was significantly lower and serum intact parathyroid hormone (PTH) was significantly higher in the African-American compared with the white women, whereas serum total calcium, Ca²⁺, phosphorus and 1,25-dihydroxyvitamin D [1,25(OH)₂D] were not different in the two groups. Serum intact PTH increased significantly at night in the white women and did not change in the African-American women. Urinary calcium was 47% lower in the African-American than in the white women during the day but was not different at night. Urinary calcium declined at night by 53% in the white women and by 40% in the African-American women. Stepwise multivariate analysis showed that determinants of urinary calcium were mean 24 h serum intact PTH and serum Ca²⁺ in the two groups together, mean 24 h serum intact PTH, body mass index (BMI) and serum 25(OH)D in the white women, and BMI in the African-American women. Urinary N-telopeptide of type I collagen, a marker of bone resorption, increased by over 60% at night in both groups and was 25% lower in African-American compared with white women, but the difference was not statistically different. Urinary free deoxypyridinoline also increased at night in both groups and was not racially different. Thus, African-American women show higher serum intact PTH and greater conservation of calcium than white women throughout the day. In both groups, maintenance of serum calcium at night is achieved by increased bone resorption and renal conservation of calcium. Received: 15 April 1999 / Accepted: 6 July 1999     

骨质疏松症患者血清骨代谢标志物分析与相关性研究

目的对西安地区部分骨质疏松症患者血清骨代谢标志物进行统计及相关性分析。方法纳入2018年4月至2019年3月经西安市红会医院诊治的原发性骨质疏松症患者295例,检测受试者血清钙(Ca)、磷(P)、碱性磷酸酶(ALP)、维生素D(vitamin D,维生素D)、甲状旁腺素(PTH)、I型前胶原N端肽(P1NP)、β-胶原特殊序列(β-Cross)的水平,运用R统计语言进行统计学处理及Pearson相关性分析。结果在大多数骨质疏松症患者中血清Ca、P是正常的;有20%~30%患者ALP升高;绝大多数患者维生素D缺乏或不足;PTH异常者以升高为主,少数女性患者PTH降低;大多数绝经前女性P1NP、β-Cross正常,在少数绝经前女性及1/3男性中出现升高,小部分绝经后女性出现下降,在小部分绝经后女性中升高。女性骨质疏松症患者中,血清ALP与P1NP、ALP与PTH、维生素D与β-Cross呈正相关(P<0.05),血清Ca与β-Cross、P与ALP、P与β-Cross、P与PTH、ALP与维生素D、ALP与β-Cross、维生素D与P1NP、维生素D与PTH、P1NP与β-Cross呈负相关(P<0.05)。男性骨质疏松症患者中,血清维生素D与β-Cross呈正相关(P<0.05),血清Ca与PTH、ALP与维生素D、维生素D与P1NP、维生素D与PTH、P1NP与β-Cross呈负相关(P<0.05)。结论骨质疏松症患者维生素D缺乏或不足情况严重,了解骨代谢标志物间的相关性有助于更好地理解骨质疏松症骨代谢异常机制。     

Influence of Daily Regimen Calcium and Vitamin D Supplementation on Parathyroid Hormone Secretion

Calcium and vitamin D supplementation has been shown to reduce secondary hyperparathyroidism and play a role in the management of senile osteoporosis. In order to define the optimal regimen of calcium and vitamin D supplementation to produce the maximal inhibition of parathyroid hormone secretion, we have compared the administration of a similar amount of Ca and vitamin D, either as a single morning dose or split in two doses, taken 6 hours apart. Twelve healthy volunteers were assigned to three investigational procedures, at weekly intervals. After a blank control procedure, when they were not exposed to any drug intake, they received two calcium-vitamin D supplement regimens including either two doses of Orocal D3 (500 mg Ca and 400 IU vitamin D) 6 hours apart or one water-soluble effervescent powder pack of Cacit D3 in a single morning dose (1000 mg Ca and 880 IU vitamin D). During the three procedures (control and the two calcium-vitamin D supplementations), venous blood was drawn every 60 minutes for up to 9 hours, for serum Ca and serum PTH measurements. The order of administration of the two Ca and vitamin D supplementation sequences was allocated by randomization. No significant changes in serum Ca were observed during the study. During the 6 hours following Ca and vitamin D supplementation, a statistically significant decrease in serum PTH was observed with both regimens, compared with baseline and with the control procedure. Over this period of time, no differences were observed between the two treatment regimens. However, between the sixth and the ninth hour, serum PTH levels were still significantly decreased compared with baseline with split dose Orocal D3 administration, while they returned to baseline value with the Cacit D3 preparation. During this period, the percentage decrease in serum PTH compared with baseline was significantly more pronounced with Orocal D3 than with Cacit D3 (P = 0.0021). We therefore conclude that the administration of two doses of 500 mg of calcium and 400 IU of vitamin D3 6 hours apart provides a more prolonged decrease in serum PTH levels than the administration of the same total amount of Ca and vitamin D as a single morning dose in young healthy volunteers. This might have implications in terms of protection of the skeleton against secondary hyperparathyroidism and increased bone resorption and turnover in elderly subjects.     

Randomized Controlled Trial of the Effects of Calcium With or Without Vitamin D on Bone Structure and Bone‐Related Chemistry in Elderly Women With Vitamin D Insufficiency

There are few data on the relative effects of calcium supplementation with or without extra vitamin D on BMD in patients selected for low vitamin D status. The aim of this study is to evaluate the relative importance of vitamin D and calcium treatment on BMD and bone‐related chemistry in elderly women with vitamin D insufficiency. Three hundred two elderly women (age, 77.2 ± 4.6 yr) with serum 25(OH)D concentrations <60 nM participated in a 1‐yr randomized, double‐blind, placebo‐controlled trial. All subjects received 1000 mg calcium citrate per day with either 1000 IU ergocalciferol (vitamin D₂) or identical placebo (control). The effects of time and time treatment interactions were evaluated by repeated‐measures ANOVA. At baseline, calcium intake was 1100 mg/d, and 25(OH)D was 44.3 ± 12.9 nM; this increased in the vitamin D group by 34% but not the control group after 1 year (59.8 ± 13.8 versus 45.0 ± 13.3 nM, p < 0.001). Total hip and total body BMD increased significantly, and procollagen type I intact N‐terminal propeptide (PINP) decreased during the study with no difference between the treatment groups (hip BMD change: vitamin D, +0.5%; control, +0.2%; total body BMD change: vitamin D, +0.4%; control, +0.4%; PINP change: vitamin D, ?3.9%; placebo, ?2.8%). Although the fasting plasma and urine calcium increased in both groups equally, there was no detectable change in serum PTH. The increase in 25(OH)D achieved with vitamin D supplementation had no extra effect on active fractional intestinal calcium absorption, which fell equally in both groups (vitamin D, ?17.4%; control, ?14.8%). In patients with a baseline calcium intake of 1100 mg/d and vitamin D insufficiency, vitamin D₂ 1000 IU for 1 year has no extra beneficial effect on bone structure, bone formation markers, or intestinal calcium absorption over an additional 1000 mg of calcium. Vitamin D supplementation adds no extra short‐term skeletal benefit to calcium citrate supplementation even in women with vitamin D insufficiency.     

The effect of risedronate treatment on serum cytokines in postmenopausal osteoporosis: a 6-month randomized and controlled study

There is much evidence suggesting that the decline in ovarian function after menopause is associated with spontaneous increases in proinflammatory cytokines. Treatment with risedronate is accompanied by significant changes in bone turnover and bone mineral density. The objective of this study was to determine the effects of risedronate treatment on the level of serum cytokines including receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin among postmenopausal women with osteoporosis. The study group consisted of 61 postmenopausal women with osteoporosis. Patients were randomly divided in two groups: In group 1 (n = 41) postmenopausal women received oral risedronate (35 mg/week), calcium (1,000 mg/day), and vitamin D (400 IU/day) for 12 months. In group 2 (control group; n = 20) patients received only oral calcium (1,000 mg/day) and vitamin D (400 IU/day). Bone mineral density (BMD) of lumbar spine (L1–L4) and proximal femur were determined using dual X-ray absorptiometry at baseline and after one year. Venous blood samples were obtained for determination of serum cytokines including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), RANKL, osteoprotegerin, and markers of bone formation and resorption. Levels of serum cytokines were measured before therapy and after three and 6 months. Markers of bone metabolism were studied before therapy and after 6 months. In group 1 (risedronate plus calcium/vitamin D-treated patients), serum levels of RANKL and IL-1β significantly decreased and the level of osteoprotegerin significantly increased after three and 6 months, but no significant difference was found in TNF-α level. In group 2, however, the level of serum cytokines did not change after three and 6 months. In cases of bone turnover, both markers of bone resorption and formation significantly decreased after 6 months in group 1. In conclusion risedronate could improve osteoporosis by increasing osteoprotegerin and reducing RANKL and IL-1β.     

ED-71, a vitamin D analog, is a more potent inhibitor of bone resorption than alfacalcidol in an estrogen-deficient rat model of osteoporosis

Although active vitamin D is used in certain countries for the treatment of osteoporosis, the risk of causing hypercalcemia/hypercalciuria means that there is only a narrow therapeutic window, and this has precluded worldwide approval. The results of our previous animal studies have suggested that the therapeutic effect of active vitamin D on bone loss after estrogen deficiency can be dissociated at least partly from its effect of enhancing intestinal calcium absorption and suppressing parathyroid hormone (PTH) secretion. To test this, we compared the effects of ED-71, a hydroxypropoxy derivative of 1alpha,25-dihydroxyvitamin D3, with orally administered alfacalcidol, on bone mineral density (BMD) and the bone remodeling process as a function of their effects on calcium metabolism and PTH, in a rat ovariectomy (ovx) model of osteoporosis. ED-71 increased bone mass at the lumbar vertebra to a greater extent than alfacalcidol, while enhancing calcium absorption (indicated by urinary calcium excretion) and decreasing serum PTH levels to the same degree as alfacalcidol. ED-71 lowered the biochemical and histological parameters of bone resorption more potently than alfacalcidol, while maintaining bone formation markers. These results suggest that active vitamin D exerts an antiosteoporotic effect by inhibiting osteoclastic bone resorption while maintaining osteoblastic function, and that these anticatabolic/anabolic effects of active vitamin D take place independently of its effects on calcium absorption and PTH. The demonstration that ED-71 is more potent in these properties than alfacalcidol makes it an attractive candidate as an antiosteoporotic drug.