25-hydroxyvitamin-d-2 and Osteoporosis--Postmenopausal

Ensuring adequate vitamin D status in older adults may reduce the risk of osteoporosis. The serum 25-hydroxyvitamin D [25(OH)D] concentration is the recommended biomarker of vitamin D status, but the optimal serum 25(OH)D concentration for bone health in postmenopausal women remains unclear.. The aim of this study was to apply the highly sensitive (41)Ca skeletal labeling technique and the measurement of urinary (41)Ca:(40)Ca ratios to determine the serum 25(OH)D concentration that has greatest benefit on bone calcium flux in postmenopausal women.. We administered a mean intravenous (41)Ca dose of 870 pmol to healthy postmenopausal women [n = 24, age (mean ± SD): 64 ± 6.0 y] without osteoporosis. After 6 mo, at the nadir of their wintertime serum 25(OH)D status, each of the women sequentially consumed daily oral cholecalciferol supplements of 10, 25, and 50 μg/d (in this order), each for 3 mo. We assessed serum 25(OH)D concentrations monthly and urinary (41)Ca:(40)Ca ratios biweekly. (41)Ca:(40)Ca ratios were measured with low-energy accelerator mass spectrometry. With the use of pharmacokinetic analysis, we determined the effect of varying serum 25(OH)D concentrations on (41)Ca transfer rates.. At baseline, the mean (95% CI) serum 25(OH)D concentration was 16.2 (13.5, 18.8) μg/L. After the first, second, and third intervention periods, mean (95% CI) serum 25(OH)D increased to 29.8 (27.2, 32.4), 36.9 (34.2, 39.7), and 46.6 (41.2, 52.0) μg/L, respectively. Supplementation was associated with a downward shift in the urinary (41)Ca:(40)Ca ratio compared with the predicted (41)Ca:(40)Ca ratio without vitamin D supplementation. In the model, the most likely site of action of the increase in serum 25(OH)D was transfer from the central compartment to a fast exchanging compartment. At this transfer rate, predicted values were a concentration with half-maximal effect of 2.33 μg/L and an estimate of the maximal effect of 31.7%. After the first, second, and third intervention periods, the mean changes in this transfer rate were +18.0%, +25.7%, and +28.5%, respectively.. In healthy postmenopausal women, increasing serum 25(OH)D primarily affects calcium transfer from the central compartment to a fast exchanging compartment; it is possible that this represents transfer from the extracellular space to the surface of bone. A serum 25(OH)D concentration of ~40 μg/L achieves ~90% of the expected maximal effect on this transfer rate. This trial was registered at clinicaltrials.gov as NCT01053481.

Topics: 25-Hydroxyvitamin D 2; Aged; Biomarkers; Bone Density Conservation Agents; Bone Remodeling; Calcifediol; Calcium; Calcium Radioisotopes; Cholecalciferol; Cohort Studies; Dietary Supplements; Down-Regulation; Female; Humans; Kinetics; Middle Aged; Osteoporosis, Postmenopausal; Risk Factors; Seasons; Switzerland

Osteoporosis is a major health issue facing postmenopausal women. Increased production of pro-inflammatory cytokines resulting from declining estrogen leads to increased bone resorption. Nutrition can have a positive impact on osteoporosis prevention and amelioration. The objective of this study was to investigate the impact of targeted phytochemicals and nutrients essential for bone health on bone turnover markers in healthy postmenopausal women. In this 14-week, single-blinded, 2-arm placebo-controlled pilot study, all women were instructed to consume a modified Mediterranean-style low-glycemic-load diet and to engage in limited aerobic exercise; 17 randomized to the placebo and 16 to the treatment arm (receiving 200 mg hop rho iso-alpha acids, 100 mg berberine sulfate trihydrate, 500 IU vitamin D(3) and 500 microg vitamin K(1), twice daily). Thirty-two women completed the study. Baseline nutrient intake did not differ between arms. At 14 weeks, the treatment arm exhibited an estimated 31% mean reduction (P = 0.02) in serum osteocalcin (a marker of bone turnover), whereas the placebo arm exhibited a 19% increase (P = 0.03) compared to baseline. Serum 25-hydroxyvitamin D (25(OH)D) increased by 13% (P = 0.24) in the treatment arm and decreased by 25% (P < 0.01) in the placebo arm. The between-arm differences for OC and 25(OH)D were statistically significant. Serum IGF-I was increased in both arms, but the increase was more significant in the treatment arm at 14 weeks (P < 0.01). Treatment with hop rho iso-alpha acids, berberine sulfate trihydrate, vitamin D(3) and vitamin K(1) produced a more favorable bone biomarker profile that supports a healthy bone metabolism.

Topics: 25-Hydroxyvitamin D 2; Berberine; Biomarkers; Bone Density Conservation Agents; Bone Remodeling; Calcifediol; Cholecalciferol; Dietary Supplements; Female; Humans; Humulus; Insulin-Like Growth Factor I; Middle Aged; Osteocalcin; Osteoporosis, Postmenopausal; Phytotherapy; Pilot Projects; Plant Extracts; Postmenopause; Single-Blind Method; Vitamin K 1

Serum 25-hydroxyvitamin D (25OHD) concentrations greater than 30 ng/ml have been recommended for lowering fracture risk.. Our objective was to determine whether 25OHD sufficiency is a prerequisite for effective response to teriparatide (TPTD).. Data were from 1620 osteoporotic postmenopausal women in the Fracture Prevention Trial. The response to TPTD was assessed in women subgrouped by having 25OHD insufficiency (>10 but 30 but 0.10). However, it should be noted that because of the limited number of fractures, this study does not exclude the possibility of differences in fracture outcome between the subgroups.. In postmenopausal women with osteoporosis and normal intact PTH, the responses to TPTD did not differ significantly in women with baseline 25OHD insufficiency or sufficiency.

Topics: 25-Hydroxyvitamin D 2; Aged; Biomarkers; Bone Density; Bone Density Conservation Agents; Bone Development; Calcifediol; Calcium; Collagen Type I; Double-Blind Method; Female; Fractures, Bone; Humans; Middle Aged; Nutritional Status; Osteoporosis, Postmenopausal; Radiography; Risk Reduction Behavior; Spinal Fractures; Teriparatide; Vitamin D Deficiency

Five years ago we reported results from a cross-sectional study of the effect of nutritional factors on calcium-regulating hormones and bone loss in perimenopausal women. We found an inverse correlation between serum 25-hydroxyvitamin D (25OHD) and immunoreactive parathyroid hormone (PTH), and we postulated that over time, women with lower 25OHD would lose more bone because of increased bone remodeling induced by secondary hyperparathyroidism. We have followed 38 of these women for 5 years. Twenty-two have gone through menopause and we are reporting observations on these 22 subjects. Bone mineral analysis was performed twice a year at the distal and mid-radius using single-photon absorptiometry. The slope of the bone mineral content curve was calculated by least squares. Bone loss increased within 6 months of the rise in serum follicle stimulating hormone (FSH) to greater than 40 mIU/ml. We continued to see a negative correlation between 25OHD and PTH (r = -0.450, P = 0.03). Premenopause, PTH was negatively correlated with the proximal bone mineral content (PBMC) slope (-0.604, P = 0.002). The distal bone mineral content (DBMC) 5-year slope was correlated with dietary vitamin D (r = 0.509, P = 0.02), the higher the intake, the less negative the slope. The 5-year PBMC slope was negatively correlated with serum osteocalcin (OC) levels (r = -0.382, P = 0.08). Before menopause, the change in PBMC was positively correlated with OC (r = 0.450, P = 0.03). Postmenopause, the correlation with DBMC slope was negative (r = -0.506, P = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 25-Hydroxyvitamin D 2; Absorptiometry, Photon; Administration, Oral; Adult; Ascorbic Acid; Bone Density; Calcifediol; Calcium; Cross-Sectional Studies; Estrogens; Female; Follicle Stimulating Hormone; Food, Fortified; Humans; Middle Aged; Minerals; Osteocalcin; Osteoporosis, Postmenopausal; Parathyroid Hormone; Phosphorus; Radius; Time Factors; Vitamin D

Vitamin K (VK) as well as vitamin D (VD) plays an important role in osteoporosis. Vitamin K1 (VK1), vitamin K2 (VK2, menaquinone-4 (MK-4), and menaquinone-7 (MK-7)) are significant for the metabolism of skeletal muscle. 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 (25(OH)D2 and 25(OH)D3) reflect circulating VD levels. More sensitive measurements remain to be developed. In the present study, a new high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the determination of VK1, VK2 (MK-4 and MK-7), as well as 25(OH)D2 and 25(OH)D3 levels in human serum.. We developed a simple LC-MS/MS method for the determination of VK1, MK-4, MK-7, 25(OH)D2, and 25(OH)D3 levels in human serum and validated the method in a study cohort of 200 patients divided into the premenopausal women group and postmenopausal osteoporosis patient group.. The overall precision (coefficient of variation) ranged from 2.66 to 10.11% in the specified working range (0.05-5 ng/mL) for VK1, MK-4, and MK-7. Serum VK1, MK-4, and MK-7 levels in postmenopausal women with osteoporosis were 1.187 ± 0.094 ng/mL, 0.058 ± 0.009 ng/mL, and 0.885 ± 0.064 ng/mL, respectively (mean ± standard deviation). Serum VK1, MK-4, and MK-7 levels in premenopausal women were 1.143 ± 0.103 ng/mL, 0.028 ± 0.003 ng/mL, and 1.553 ± 0.226 ng/mL, respectively. Serum 25(OH)D2 and 25(OH)D3 levels in postmenopausal women with osteoporosis were 0.757 ± 0.056 ng/mL and 11.72 ± 0.632 ng/mL, respectively. Serum 25(OH)D2 and 25(OH)D3 levels in premenopausal were 1.793 ± 0.575 ng/mL and 12.42 ± 1.069 ng/mL, respectively.. A new LC-MS/MS method for determination of serum VK and VD levels was evaluated and validated. MK-7 in plasma decreased earlier than VD in postmenopausal osteoporosis patients. MK-7 status is significantly associated with osteoporosis and could be considered a predictable biomarker in the diagnosis of osteoporosis in postmenopausal women.

Topics: 25-Hydroxyvitamin D 2; Calcifediol; Chromatography, Liquid; Female; Humans; Osteoporosis; Osteoporosis, Postmenopausal; Tandem Mass Spectrometry; Vitamin D; Vitamin K 1; Vitamins

This study aimed to discover genetic variants in the entire 101 kB vitamin D receptor (VDR) gene for vitamin D deficiency in a group of postmenopausal Filipino women using targeted next generation sequencing (TNGS) approach in a case-control study design. A total of 50 women with and without osteoporotic fracture seen at the Philippine Orthopedic Center were included. Blood samples were collected for determination of serum vitamin D, calcium, phosphorus, glucose, blood urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase and as primary source for targeted VDR gene sequencing using the Ion Torrent Personal Genome Machine. The variant calling was based on the GATK best practice workflow and annotated using Annovar tool. A total of 1496 unique variants in the whole 101-kb VDR gene were identified. Novel sequence variations not registered in the dbSNP database were found among cases and controls at a rate of 23.1% and 16.6% of total discovered variants, respectively. One disease-associated enhancer showed statistically significant association to low serum 25-hydroxy vitamin D levels (Pearson chi-square P-value=0.009). The transcription factor binding site prediction program PROMO predicted the disruption of three transcription factor binding sites in this enhancer region. These findings show the power of TNGS in identifying sequence variations in a very large gene and the surprising results obtained in this study greatly expand the catalog of known VDR sequence variants that may represent an important clue in the emergence of vitamin D deficiency. Such information will also provide the additional guidance necessary toward a personalized nutritional advice to reach sufficient vitamin D status.

Topics: 25-Hydroxyvitamin D 2; Aged; Aging; Calcifediol; Case-Control Studies; Computational Biology; Female; Genetic Association Studies; Genetic Predisposition to Disease; High-Throughput Nucleotide Sequencing; Humans; Incidence; Middle Aged; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Philippines; Pilot Projects; Polymorphism, Single Nucleotide; Receptors, Calcitriol; Risk Factors; Vitamin D Deficiency; Vitamin D Response Element

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

An evidence-based guideline on the use of intravenous (i.v.) bisphosphonates in post-menopausal osteoporosis was developed across a healthcare system and approved by clinical experts and Pharmacy and Therapeutics Committees. The objective of the study was to evaluate adherence to the guideline at hospitals in the healthcare system.. Post-menopausal women who received i.v. zoledronic acid or i.v. ibandronate for osteoporosis between September 2007 and October 2008 were identified through a data repository that provides patient-level longitudinal information on diagnoses, medications and laboratory tests. Manual review of electronic medical records supplemented the data capture. The guideline recommends use of i.v. bisphosphonates in patients: (i) who have had a recent vertebral or hip fracture; (ii) who cannot stand or sit upright for 30-60 min; (iii) who have oesophageal dysmotility or varices; (iv) who have documented adherence issues or, (v) who failed to tolerate oral bisphosphonates after 12 months. In addition, specific monitoring tests are recommended prior to administration.. Among the 220 women that received an i.v. bisphosphonate (hospitals A/B: n = 92 vs. hospital C: n = 128), 72% met the criteria for use. The results were similar when examined by institution (hospitals A/B 66% vs. hospital C 77%; P = 0·094). On review of the electronic medical records, an additional reason for using i.v. bisphosphonates was identified: persistent bone loss despite oral bisphosphonate therapy. When this criterion for use was included, the adherence rate increased to 80% (hospitals A/B 72% vs. hospital C 86%; P = 0·009). Serum calcium and 25-OH vitamin D were performed in 75% (hospitals A/B 77% vs. hospital C 73%; P = 0·53), and 86% (hospitals A/B 84% vs. hospital C 87%; P = 0·53) of patients respectively.. Adherence to an i.v. bisphosphonates evidence-based guideline was adequate (defined as at least 80%) although room for improvement in meeting the criteria for use at one hospital and for conducting baseline serum calcium levels was noted. A future project is warranted to re-assesses adherence after the measures to improve guideline adherence are implemented.

Topics: 25-Hydroxyvitamin D 2; Aged; Bone Density Conservation Agents; Calcifediol; Calcium; Consensus; Diphosphonates; Drug Resistance; Electronic Health Records; Evidence-Based Medicine; Female; Guideline Adherence; Humans; Ibandronic Acid; Imidazoles; Injections, Intravenous; Longitudinal Studies; Middle Aged; Osteoporosis, Postmenopausal; Practice Guidelines as Topic; Zoledronic Acid

We obtained serum bone markers and other relevant endocrine assays on 5 patients with osteonecrosis of the jaw (ONJ). The assays were C-telopeptide, N-telopeptide, bone-specific alkaline phosphatase, osteocalcin, intact parathyroid hormone, T3, T4, TSH, and Vitamin D 25 hydroxy. Diagnostic criteria for ONJ were those formulated by the American Association of Oral and Maxillofacial Surgeons. Four of our patients were women. Two had metastatic breast cancer and had been treated with zoledronic acid; one had also received pamidronate. Two others had osteoporosis and had been treated with daily alendronate. One man had metastatic prostate cancer treated with zoledronic acid. All patients had been withdrawn from bisphosphonate for at least 6 months. None were taking or had taken corticosteroids. None of the lesions had shown any significant healing and all were still causing the patients considerable distress. Yet the bone markers were within the normal range as measured in our laboratory, except for intact parathyroid hormone, which was slightly elevated in one case of metastatic breast cancer (177 pg/mL). Because the jaws have a greater blood supply than other bones, and a high bone turnover rate, bisphosphonates are highly concentrated in the jaws. This anatomic concentration of bisphosphonates might cause bisphosphonate-osteonecrosis to be manifested exclusively in the jaws and is consistent with our finding of normal serum bone markers in ONJ patients.

Topics: 25-Hydroxyvitamin D 2; Alkaline Phosphatase; Bone Density Conservation Agents; Bone Neoplasms; Breast Neoplasms; Collagen Type I; Diphosphonates; Female; Humans; Jaw Diseases; Male; Osteocalcin; Osteonecrosis; Osteoporosis, Postmenopausal; Parathyroid Hormone; Peptides; Prostatic Neoplasms

Topics: 25-Hydroxyvitamin D 2; Absorptiometry, Photon; Aged; Alendronate; Alkaline Phosphatase; Back Pain; Bone Density; Calcium; Ergocalciferols; Female; Humans; Lumbar Vertebrae; Osteomalacia; Osteoporosis, Postmenopausal; Treatment Outcome

Few studies of vitamin D nutrition in Asian populations have been conducted.. The objective was to assess 25-hydroxyvitamin D [25(OH)D] concentrations in healthy elderly Japanese women during the winter and to determine whether 25(OH)D concentrations are associated with lifestyle.. We investigated 151 women aged 66.5 +/- 6.7 y (f1.gif" BORDER="0"> +/- SD) living in a rural community in February 1999. Serum 25(OH)D and intact parathyroid hormone were measured by using HPLC and an immunoradiometric assay, respectively. Information on lifestyle factors, including sunshine exposure and the consumption of vitamin D-rich foods, was also obtained through an interview.. The mean (+/-SD) 25(OH)D concentration was 59.9 +/- 17.0 nmol/L. Vitamin D insufficiencies (<30 nmol/L) were found in 4.6% of the women, a value lower than that found in white populations. No correlation was found between age and 25(OH)D concentrations (r = 0.004, P = 0.957). The 25(OH)D concentration of subjects who consumed fish frequently (>/=4 times/wk) was 10.1 nmol/L higher (P < 0.001) than that of subjects with a moderate consumption of fish (1-3 times/wk). Additionally, those who did not consume eggs had significantly lower 25(OH)D concentrations than did those who consumed eggs >/=1 time/wk (P < 0.05).. : The nutritional status of vitamin D in Japanese populations seems to be better than that in most Western populations. Frequent fish consumption is believed to help maintain adequate concentrations of serum 25(OH)D in elderly Japanese women during the winter.

Topics: 25-Hydroxyvitamin D 2; Agaricales; Aged; Aged, 80 and over; Animals; Calcifediol; Chromatography, High Pressure Liquid; Eggs; Female; Fishes; Humans; Japan; Middle Aged; Osteoporosis, Postmenopausal; Parathyroid Hormone; Postmenopause; Premenopause; Radioimmunoassay; Rural Population; Statistics, Nonparametric; Sunlight; Vitamin D Deficiency

The present study was designed to visit elderly women living in nursing homes and to compare their femoral neck bone mineral density (BMD) and circulating levels of parathyroid hormone (PTH) and 25-OH vitamin D (25-OHD) with those of subjects living at home, in the immediate vicinity of the nursing homes. Of 1483 women, aged 70 years and older, who were selected, 993 agreed to participate in this trial. Their femoral neck BMD (n = 993) was measured by dual-energy X-ray absorptiometry, with a specific device installed in a mobile truck. The circulating levels of 25-OHD and PTH were assessed after an overnight fast (n = 748). After stratification for age, there were no significant differences in mean femoral neck BMD values, prevalence of femoral neck osteoporosis, mean serum 25-OHD and prevalence of absolute or relative 25-OHD deficiency between the two groups. Serum levels of PTH were significantly higher in women over 80 years old living in nursing homes, compared with the community-dwelling women. After adjustment for age, a significant relation was found between femoral neck BMD and PTH levels in the whole population (p = 0.004) and in community-dwelling subjects (p = 0.039). When stratifying our population by quartiles of serum PTH values, the odds ratios for femoral neck osteoporosis were significantly increased for the top two quartiles compared with the lowest one both before (p = 0.00146) and after (p = 0.0013) adjustment for age and type of housing. From this study we conclude that femoral osteoporosis is largely underestimated in European women. Living in a nursing home is not, per se, a risk factor for decreased femoral BMD, and circulating PTH levels are a key determinant of low femoral bone density and osteoporosis.

Topics: 25-Hydroxyvitamin D 2; Absorptiometry, Photon; Aged; Aged, 80 and over; Calcium, Dietary; Female; Femur Neck; Humans; Nursing Homes; Osteoporosis, Postmenopausal; Parathyroid Hormone; Prevalence