24-25-dihydroxyvitamin-d-3 and Osteoporosis--Postmenopausal

Substantial variability exists in the serum 25(OH)D increase observed in response to vitamin D supplementation. Measurement of circulating cholecalciferol and 24,25(OH)₂D, as indicators of vitamin D absorption and degradation, respectively, account for approximately half of the variation in serum 25(OH)D observed following supplementation.. Vitamin D supplementation produces a variable response in serum 25(OH)D. This variability likely reflects, in part, differences in vitamin D absorption and/or degradation. Despite this variation in response, virtually all expert recommendations endorse a fixed vitamin D supplementation dose, an approach also used in most prospective studies. Such utilization of a single vitamin D dose does not assure attaining any pre-specified target 25(OH)D level, thereby compromising clinical care and prospective supplementation trials. This study begins addressing this weakness by exploring the feasibility of vitamin D metabolite measurements to predict serum 25(OH)D level attained following supplementation.. Ninety-one community-dwelling postmenopausal women with baseline 25(OH)D of 10-30 ng/mL received oral vitamin D₃, 2300 or 2500 IU, daily for 4-6 months. Serum 25(OH)D, cholecalciferol (D₃), and 24,25(OH)₂D were measured before and at the end of supplementation to determine if metabolite concentrations allow prediction of the 25(OH)D level attained.. From baseline and follow-up data, we derived a multiple linear regression model predicting posttreatment 25(OH)D as follows: final 25(OH)D = 8.3 + (1.05*initial 25(OH)D) - (7.7*initial 24,25(OH)₂D) + (0.53*final D₃) + (4.2*final 24,25(OH)₂D). This model has an adjusted R(2) = 0.55, thus accounting for approximately half of the observed variance in the final 25(OH)D level.. The contributions of circulating cholecalciferol and 24,25(OH)₂D to this predictive model can be considered as indicators of intestinal absorption and clearance, respectively. This paradigm requires further study; it may allow efficient "treat-to-25(OH)D-target" strategies useful in optimizing prospective studies and clinical practice.

Topics: 24,25-Dihydroxyvitamin D 3; Aged; Bone Density Conservation Agents; Cholecalciferol; Dietary Supplements; Drug Monitoring; Female; Follow-Up Studies; Humans; Middle Aged; Osteoporosis, Postmenopausal; Vitamin D

Estrogen therapy (ET) is associated with lower serum calcium and phosphorus concentrations and is known to increase bone mineral density (BMD). Other biomarkers of mineral metabolism may help understand the biological basis of these actions.. We studied 2767 postmenopausal women in the Multi-Ethnic Study of Atherosclerosis, 862 (31%) of whom were using ET. We measured serum concentrations of calcium, phosphorus, 25-hydroxyvitamin D, 24,25-dihydoxyvitamin D, and fibroblast growth factor-23 and urinary fractional excretion of calcium (FEca) and phosphorus (FEphos). We examined the associations of ET with each biomarker. In addition, we tested whether the adjustment for biomarkers attenuated the association of ET with lumbar BMD measured by abdominal computed tomography in a subset of 810 women.. In adjusted models, women who used ET were younger in age [62 (SD 8) vs 66 (9) y, P < .001], had lower mean serum calcium [-13 mg/dL (95% confidence interval [CI] -0.17, -0.10), P < .001] and lower FEca [-0.15% (95% CI -0.21, -0.09), P < .001]. Mean serum phosphorus was lower [-0.19 mg/dL (95% CI -0.23, -0.15), P < .001] and FEphos [0.56% (95% CI 0.16, 0.96), P = .007] was higher in women on ET. Mean 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D were higher [1.52 ng/dL (95% CI 0.57, 2.47), P = .002, and 0.26 ng/mL (95% CI 0.03, 0.48), P = .03, respectively] in women who used ET. Mean PTH and fibroblast growth factor-23 did not differ significantly by the use of ET. ET use was strongly associated with higher lumbar BMD [12.75 mg/cm³ (95% CI 7.77-17.73), P < .001]; however, mineral metabolism measures did not meaningfully alter this association.. In a multiethnic cohort of postmenopausal women, ET use was associated with lower serum calcium, lower FEca, lower serum phosphorus, and higher FEphos, suggesting these associations are attributable to increased calcium intake into bone and increased urinary phosphorus excretion. ET use was also associated with greater concentrations of vitamin D metabolites. ET-associated differences in these mineral metabolism measures did not meaningfully attenuate the strong association between ET use and lumbar BMD.

Topics: 24,25-Dihydroxyvitamin D 3; 25-Hydroxyvitamin D 2; Aged; Aged, 80 and over; Biomarkers; Bone and Bones; Bone Density; Calcifediol; Calcium; Cohort Studies; Cross-Sectional Studies; Ergocalciferols; Estrogen Replacement Therapy; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Middle Aged; Osteoporosis, Postmenopausal; Phosphorus; Radiography; Vitamin D

Comparative study results of vitamin's D active metabolites 1,25-dihydroxycholecalciferol (1,25(OH)2D3) and 24,25-dihydroxycholecalciferol (24,25(OH)2D3) effect on ionised calcium level in blood plasma of patients with postmenopause osteoporosis are described. Administration of 24,25(OH)2D3 for patients with osteoporosis leads to gradual stepped increase of ionised calcium level in blood plasma. This level remains normal and does not change in 2 weeks after cancelling of drug administration. Prescription of 1,25(OH)2D3 rapidly increases ionised calcium level in blood plasma and it's cancelling leads to normalisation of ionized calcium concentration in blood plasma during 1 week. Combination of two medicines causes summation of their effects. Administration of 24,25(OH)2D3 (10 mcg per 24 hours) and 1,25(OH)2D3 (0.5 mcg per 24 hours) doesn't cause any of incidental and allergic reactions.

Topics: 24,25-Dihydroxyvitamin D 3; Administration, Oral; Aged; Calcitriol; Calcium; Cations, Divalent; Female; Humans; Middle Aged; Osteoporosis, Postmenopausal; Postmenopause

To examine changes in mechanical competence of bone caused by ovariectomy, and to assess the effect of 24R,25-dihydroxyvitamin D3 (24R,25(OH)2D3) administration on mass and structure, we conducted mechanical tests on canine lumbar vertebrae and femur 31 months after surgery. Beagles weighing 9-10 kg were ovariectomized (OVX) or sham operated (n = 3, group 1). OVX dogs were divided into three groups. Group 2 (n = 3) received only the agent vehicle, groups 3 (n = 4) and 4 (n = 4) received daily 24R,25(OH)2D3 doses of 2 and 10 mcg/kg, respectively from 1 month after surgery. In group 4, the dose level was increased up to 100 mcg/kg by the 17 month. Then, L3 and L4 vertebrae and left femur were excised from each animal. Torsional tests at the femoral diaphysis were conducted. On the L3 specimen, the circumferential shell was removed to obtain a cancellous core specimen. The shell was left intact on the L4 specimen. In compression tests, the loading was stopped just after maximal strength was reached for minimum specimen collapse, from which 7-mcm thick, undecalcified, midcross sections parallel to the base of the specimen were obtained. Neither femoral morphology, bone mineral contents (BMCs) nor structural stiffness indicated a significant difference among groups. Though L3 and L4 BMCs were reduced in group 2, in group 3 and 4 they were significantly larger than in group 2. Compression tests on lumbar vertebral specimens showed a significant decrease in mechanical parameters in group 2. On the cancellous core specimen of L3, the mean structural stiffness in group 2 was 31.8% of that in group 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 24,25-Dihydroxyvitamin D 3; Analysis of Variance; Animals; Biomechanical Phenomena; Bone and Bones; Bone Density; Disease Models, Animal; Dogs; Female; Femur; Humans; Lumbar Vertebrae; Osteoporosis, Postmenopausal; Ovariectomy; Stress, Mechanical

In order to determine whether the administration of 24R,25(OH)2D3 had any beneficial effect on the regulation of bone turnover and the prevention of bone atrophy, we examined beagles for 31 months after ovariectomy (OVX). Fourteen beagle dogs (8.54 +/- 1.22 kg body wt-b.w.) were divided into four groups. Group 1 (n = 3) was the sham, and Group 2 (n = 3) served as the OVX control. In Group 3 (n = 4) and Group 4 (n = 4), 24,25-dihydroxyvitamin D3(24R,25(OH)2D3) was given daily at dose levels of 2 and 10 mcg/kg B.W., respectively. In Group 4, the dose level was increased to 100 mcg/kg by 17 months. During the experiments, urinary hydroxyproline (U-HPr), serum chemistry, serum bone gla-protein (BGP), and vitamin D metabolite levels were monitored. At the end of the experiment, bone mineral content (BMC) in the 6th and 7th lumbar vertebrae and right femur was determined by single photon absorptiometry. The left iliac bone sample was obtained after tetracycline labeling, and undecalcified sections were observed. In Group 2, excretion of U-HPr increased after OVX and had reached a level of approximately twice the baseline values by 10 months; then it gradually came down to the original level. In Group 3, however, U-HPr excretion remained at the same level as the baseline value, as it did in Group 1. In Group 4, it was remarkably reduced down to 50-60% of the baseline values. Serum BGP level was markedly reduced in Group 4. Serum 24,25(OH)2D levels were markedly increased in Groups 3 and 4.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 24,25-Dihydroxyvitamin D 3; Animals; Bone and Bones; Bone Resorption; Disease Models, Animal; Dogs; Drug Evaluation, Preclinical; Female; Humans; Hydroxyproline; Ilium; Osteocalcin; Osteoclasts; Osteoporosis, Postmenopausal; Ovariectomy

We studied 20 healthy premenopausal women aged 36.5 +/- 4.0 years (mean +/- 1 SD), 123 healthy postmenopausal women aged 50.0 +/- 2.4 years, and 103 postmenopausal women aged 65.1 +/- 5.6 years with symptomatic osteoporosis (forearm and spinal fracture). Serum levels of vitamin D metabolites [25(OH)D, 24,25(OH)2D3, and 1,25-(OH)2D] were compared with (1) bone mass in the forearm (single photon absorptiometry) and in the spine (dual photon absorptiometry); (2) biochemical indices of bone formation (serum alkaline phosphatase, plasma bone Gla protein), and bone resorption (fasting urinary hydroxyproline); and (3) other biochemical estimates of calcium metabolism (serum calcium, serum phosphate, 24-hour urinary calcium, intestinal absorption of calcium). The present study revealed no difference in any of the vitamin D metabolites between the premenopausal women, the healthy postmenopausal women and the osteoporotic women as a group. The concentrations of 1,25(OH)2D and 25(OH)D were significantly lower in patients with spinal fracture than in those with forearm fracture. In the early postmenopausal women serum 1,25(OH)D was related to forearm bone mass (r = -0.20; P less than 0.05), intestinal calcium absorption (r = 0.18; P less than 0.05), and 24-hour urinary calcium (r = 0.21; P less than 0.05); serum 25(OH)D was related to spinal bone mass (r = 0.23; P less than 0.01). In the osteoporotic women, serum vitamin D metabolites were not related to bone mass, but 1,25(OH)2D was related to bone Gla protein (r = 0.33; P less than 0.001), serum phosphate (r = -0.27; P less than 0.01), and 24-hour urinary calcium (r = 0.43; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 24,25-Dihydroxyvitamin D 3; Absorptiometry, Photon; Adult; Aging; Alkaline Phosphatase; Bone and Bones; Bone Density; Calcitriol; Calcium; Female; Humans; Hydroxyproline; Intestinal Absorption; Intestinal Mucosa; Middle Aged; Osteocalcin; Osteoporosis, Postmenopausal; Phosphates; Vitamin D

We investigated the influence of menopause, age and sex on vitamin D metabolism in a large group of healthy women (n = 113) and men (n = 108) and in a group of early postmenopausal women (n = 124). Furthermore, we studied the vitamin D metabolism in 42 women with endometriosis. The vitamin D metabolites did not show dependence on age or on duration of menopause. The serum concentrations of vitamin D metabolites did not differ in normal men and women. There were highly significant seasonal oscillations for 25(OH)D and 24,25(OH)2D3 but not for 1,25(OH)2D. Women with endometriosis had significantly elevated serum 1,25(OH)2D compared to the normal women. Our study indicates that ageing is not associated with a significant depletion of 25(OH)D, 24,25(OH)2D or 1,25(OH)2D in normal men and women up to the age of 75 years. Furthermore, changes in vitamin D metabolism seem not to be an important factor in early postmenopausal bone loss. Our results on patients with endometriosis indicate that these patients may have some calcium-metabolic disturbances.

Topics: 24,25-Dihydroxyvitamin D 3; Adult; Aged; Aging; Calcifediol; Calcitriol; Calcium; Endometriosis; Female; Humans; Male; Menopause; Middle Aged; Osteoporosis, Postmenopausal; Phosphates; Seasons; Vitamin D