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Vitamin D Daily versus Monthly Administration: Bone Turnover and Adipose Tissue Influences.
Dalle Carbonare, L, Valenti, MT, Del Forno, F, Piacentini, G, Pietrobelli, A
Nutrients. 2018;(12)
Abstract
Vitamin D is involved in bone metabolism and in many various extra-skeletal diseases such as malabsorption syndromes, cardiovascular and metabolic diseases, cancer, and autoimmune and neurological diseases. However, data on the optimal route of administration are not consistent. The aims of our study were to analyze not only the influence of daily vs. monthly administration of vitamin D on bone metabolism and bone turnover, but also the effects of different routes of administration on fat mass in a cohort of adults with low levels of 25(OH) vitamin D3 at baseline. We analyzed 44 patients with hypovitaminosis at baseline and after six months of two different regimens of administration: seven drops (1750 IU)/day vs. 50,000 IU/month. We found that the two regimens were equivalent; 36 out of 44 patients reached the normal range of vitamin D after six months of treatment. Interestingly, the main determinant of vitamin D at baseline was the waist circumference. In addition, 22 patients treated by monthly regimen were evaluated after 18 months of treatment. At the end of follow-up, patients showed normal levels of vitamin D, with increased calcium levels and decreased bone turnover. Waist circumference also decreased. Our results support the efficacy of vitamin D3 given monthly both for correcting hypovitaminosis and for maintaining vitamin D levels. The relationship between serum 25(OH)vitamin D3 concentration and waist circumference supports vitamin D having a protective role in the current setting, since waist size is directly associated with the risk of cardiovascular and metabolic diseases.
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Comparison of two automated assays of BTM (CTX and P1NP) and reference intervals in a Danish population.
Jørgensen, NR, Møllehave, LT, Hansen, YBL, Quardon, N, Lylloff, L, Linneberg, A
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2017;(7):2103-2113
Abstract
UNLABELLED Bone turnover markers are used for monitoring osteoporosis treatment. Therefore, we evaluated the agreement between different assays for CTX and PINP and established reference intervals in a cohort of 2300 individuals. We found poor agreement between assays and different reference intervals. This highlights the importance of harmonization of the assays. INTRODUCTION Two reference markers for bone turnover have been proposed: CTX bone resorption and P1NP for bone formation. The purpose of the current study was to establish reference intervals for the two markers in a Danish cohort and to determine the agreement on the two platforms. METHODS Fasting sera from 2308 individuals (1250 males and 1058 females, age range 24-76 years) participating in the Health2006 study were analyzed for CTX and P1NP using the automated IDS-iSYS analyzer and the automated Cobas e411 analyzer. Participants in anti-osteoporotic treatment were excluded, while subjects on hormonal contraceptives were included. RESULTS There was significant disagreement between both the two P1NP assays with a mean difference of -3 μg/L (LoA -19 to 14) (p < 0.001) and the two CTX assays with a mean difference of 13 ng/L (LoA-187 to 214) (p < 0.001). For CTX, there was a systematic bias: at low values, Cobas measured a higher value than iSYS and at higher concentrations, iSYS measured increasingly higher values than Cobas. Based on the results, we propose three reference intervals for each sex: 25-29, 30-39, and 40-80 years for men, and 25-29, >30 (pre-menopausal), and >30 years (post-menopausal) for women. CONCLUSIONS There is significant disagreement between the IDS-iSYS and Roche Cobas assays for both reference markers. Consequently, the reference intervals for an adult, healthy population are different depending on the analysis method used. Therefore, repeated measurements of patient samples used for monitoring of treatment should be done on the same assay. Moreover, assay-specific reference intervals should be used. Harmonization of assays for BTM is highly warranted.
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The effects of non-calcium-based phosphate binders versus calcium-based phosphate binders on cardiovascular calcification and bone remodeling among dialysis patients: a meta-analysis of randomized trials.
Liu, L, Wang, Y, Chen, H, Zhu, X, Zhou, L, Yang, Y
Renal failure. 2014;(8):1244-52
Abstract
BACKGROUND Vascular calcification significantly increases the rates of cardiovascular mortality in hemodialysis (HD) patients. Abnormalities in mineral metabolism may play a role in the pathogenesis of arterial calcification. Whether patients treated with non-calcium-based phosphate binders had reduced aortic vascular calcification compared to those treated with calcium-based phosphate binders is still unclear. METHODS We searched multiple databases for studies published through August 2013 that evaluated the effects of non-calcium-based phosphate binders (NCBP) versus calcium-based phosphate binders (CBP) on cardiovascular calcification and bone remodeling among dialysis patients. We summarized test performance characteristics with the use of forest plots, fixed and random effects models, and Egger regression test. RESULTS Eighteen eligible randomized controlled trials totaling 3676 patients were included. Meta-analysis results showed NCBP could significantly attenuate the progression of coronary artery calcification than CBP (WMD: -144.62, 95% CI: -285.62 to -3.63). The serum calcium levels significant lower in NCPB group than in CPB groups (WMD: -0.26, 95% CI: -0.37 to -0.14), but the serum iPTH levels were significantly higher in NCPB groups (WMD: 57.1, 95% CI: 13.42 to 100.78). The osteoid volume and osteoblast numbers were significant higher in NCPB group than in CPB group (WMD: 1.75, 95% CI: 0.78 to 2.73 for osteoid volume; WMD: 4.49, 95% CI: 1.83 to 7.15 for osteoblast numbers). The Egger regression test also showed no potential publication bias (p = 0.725). CONCLUSIONS Based on available data, NCBPs have equally effective with CBPs for serum phosphate control. But there was significantly lower incidence of coronary artery calcification and a significant higher bone formatting rate in NCBP groups than in CBP groups. So we recommend NCBPs as phosphate binders for HD patients.
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A comparison of parathyroid hormone-related protein (1-36) and parathyroid hormone (1-34) on markers of bone turnover and bone density in postmenopausal women: the PrOP study.
Horwitz, MJ, Augustine, M, Khan, L, Martin, E, Oakley, CC, Carneiro, RM, Tedesco, MB, Laslavic, A, Sereika, SM, Bisello, A, et al
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2013;(11):2266-76
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Abstract
Parathyroid hormone-related protein (PTHrP)(1-36) increases lumbar spine (LS) bone mineral density (BMD), acting as an anabolic agent when injected intermittently, but it has not been directly compared with parathyroid hormone (PTH)(1-34). We performed a 3-month randomized, prospective study in 105 postmenopausal women with low bone density or osteoporosis, comparing daily subcutaneous injections of PTHrP(1-36) to PTH(1-34). Thirty-five women were randomized to each of three groups: PTHrP(1-36) 400 µg/day; PTHrP(1-36) 600 µg/day; and PTH(1-34) 20 µg/day. The primary outcome measures were changes in amino-terminal telopeptides of procollagen 1 (PINP) and carboxy-terminal telopeptides of collagen 1 (CTX). Secondary measures included safety parameters, 1,25(OH)2 vitamin D, and BMD. The increase in bone resorption (CTX) by PTH(1-34) (92%) (p < 0.005) was greater than for PTHrP(1-36) (30%) (p < 0.05). PTH(1-34) also increased bone formation (PINP) (171%) (p < 0.0005) more than either dose of PTHrP(1-36) (46% and 87%). The increase in PINP was earlier (day 15) and greater than the increase in CTX for all three groups. LS BMD increased equivalently in each group (p < 0.05 for all). Total hip (TH) and femoral neck (FN) BMD increased equivalently in each group but were only significant for the two doses of PTHrP(1-36) (p < 0.05) at the TH and for PTHrP(1-36) 400 (p < 0.05) at the FN. PTHrP(1-36) 400 induced mild, transient (day 15) hypercalcemia. PTHrP(1-36) 600 required a dose reduction for hypercalcemia in three subjects. PTH(1-34) was not associated with hypercalcemia. Each peptide induced a marked biphasic increase in 1,25(OH)2 D. Adverse events (AE) were similar among the three groups. This study demonstrates that PTHrP(1-36) and PTH(1-34) cause similar increases in LS BMD. PTHrP(1-36) also increased hip BMD. PTH(1-34) induced greater changes in bone turnover than PTHrP(1-36). PTHrP(1-36) was associated with mild transient hypercalcemia. Longer-term studies using lower doses of PTHrP(1-36) are needed to define both the optimal dose and full clinical benefits of PTHrP. © 2013 American Society for Bone and Mineral Research.
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Nitrates and bone turnover (NABT) - trial to select the best nitrate preparation: study protocol for a randomized controlled trial.
Bucur, RC, Reid, LS, Hamilton, CJ, Cummings, SR, Jamal, SA
Trials. 2013;:284
Abstract
BACKGROUND Organic nitrates uncouple bone turnover, improve bone mineral density, and improve trabecular and cortical components of bone. These changes in turnover, strength and geometry may translate into an important reduction in fractures. However, before proceeding with a large fracture trial, there is a need to identify the nitrate formulation that has both the greatest efficacy (with regards to bone turnover markers) and gives the fewest headaches. Ascertaining which nitrate formulation this may be is the purpose of the current study. METHODS AND DESIGN This will be an open-label randomized, controlled trial conducted at Women's College Hospital comparing five formulations of nitrates for their effects on bone turnover markers and headache. We will recruit postmenopausal women age 50 years or older with no contraindications to nitroglycerin. Our trial will consist of a run-in phase and a treatment phase. We will enroll 420 women in the run-in phase, each to receive all of the 5 potential treatments in random order for 2 days, each with a 2-day washout period between treatments. Those who tolerate all formulations will enter the 12-week treatment phase and be randomly assigned to one of five groups: 0.3 mg sublingual nitroglycerin tablet, 0.6 mg of the sublingual tablet, a 20 mg tablet of isosorbide mononitrate, a 160 mg nitroglycerin transdermal patch (used for 8 h), and 15 mg of nitroglycerin ointment as used in a previous trial by our group. We will continue enrolment until we have randomized 210 women or 35 women per group. Concentrations of bone formation (bone-specific alkaline phosphatase and procollagen type I N-terminal propeptide) and bone resorption (C-telopeptides of collagen crosslinks and N-terminal crosslinks of collagen) agents will be measured in samples taken at study entry (the start of the run in phase) and 12 weeks. Subjects will record the frequency and severity of headaches daily during the run-in phase and then monthly after that. We will use the 'multiple comparisons with the best' approach for data analyses, as this strategy allows practical considerations of ease of use and tolerability to guide selection of the preparation for future studies. DISCUSSION Data from this protocol will be used to develop a randomized, controlled trial of nitrates to prevent osteoporotic fractures. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01387672. Controlled-Trials.com: ISRCTN08860742.
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Comparative evaluation of isosorbide mononitrate and alendronate in management of postmenopausal osteoporosis.
Duhan, N, Siwach, RC, Yadav, K, Dahiya, K, Nanda, S, Sirohiwal, D
Archives of gynecology and obstetrics. 2012;(4):1019-23
Abstract
BACKGROUND Osteoporosis, a skeletal disorder that adversely affects bone strength , is common among postmenopausal women primarily due to reduced ovarian estrogens. PURPOSE The present study was taken up to evaluate the role of isosorbide mononitrate (IMN) in the management of postmenopausal osteoporosis and to compare its efficacy with that of alendronate. METHODS This prospective systematic randomized study was conducted on 90 postmenopausal women with lumbar spine BMD >2.5 SD below the young adult reference range. The participants received either Tab Alendronate 70 mg orally, once weekly (Group I) or Tab IMN 40 mg orally once daily (Group II) for 9 months, in addition to 500 mg of oral calcium daily. The BMD of the lumbar spine was measured using DEXA scan at enrolment and after 9 months. The data was analyzed by Student's t test and Chi-square test. RESULTS The mean baseline BMD was 0.67 + 0.097 and 0.68 + 0.067 g/cm(2) in Group I and II, respectively. An increase of 11.94% in the mean BMD was noted after 9 months of treatment with alendronate as against 8.82% with IMN. Headache, flushing and palpitations in Group II and nausea, epigastric pain and heart burn in Group I were the most common adverse effects. CONCLUSION IMN has a beneficial effect on bone turnover in cases of postmenopausal osteoporosis and that the effect is comparable to that of alendronate. IMN is a promising and safe alternative to alendronate for the management of postmenopausal osteoporosis.
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The effects of ronacaleret, a calcium-sensing receptor antagonist, on bone mineral density and biochemical markers of bone turnover in postmenopausal women with low bone mineral density.
Fitzpatrick, LA, Dabrowski, CE, Cicconetti, G, Gordon, DN, Papapoulos, S, Bone, HG, Bilezikian, JP
The Journal of clinical endocrinology and metabolism. 2011;(8):2441-9
Abstract
CONTEXT Ronacaleret, a calcium-sensing receptor antagonist that stimulates PTH release from the parathyroid glands, was evaluated as an oral osteoanabolic agent for the treatment of osteoporosis. OBJECTIVE Our objective was to compare the effects of ronacaleret, teriparatide, and alendronate on bone mineral density (BMD) and markers of bone turnover. DESIGN AND SETTING In this randomized, placebo-controlled, dose-ranging trial, spine and hip BMD were assessed by dual-energy x-ray absorptiometry and bone turnover markers were measured. PATIENTS Patients included 569 postmenopausal women with low BMD. INTERVENTIONS Subjects were offered open-label 20 μg teriparatide sc once daily or were randomized to 100, 200, 300, or 400 mg oral ronacaleret once daily, 70 mg alendronate once weekly, or placebo and were followed for up to 12 months. MAIN OUTCOME MEASURE Percentage change from baseline in lumbar spine BMD was assessed at month 12. RESULTS With ronacaleret, the increases in lumbar spine BMD at 12 months (0.3-1.6%) were significantly lower than those attained with teriparatide (9.1%) or alendronate (4.5%). There were small decreases in total hip, femoral neck, and trochanter BMD at month 12 with ronacaleret compared with increases in the teriparatide and alendronate arms. Bone turnover markers increased in the ronacaleret and teriparatide arms and decreased in the alendronate arm. PTH elevations with ronacaleret were prolonged relative to those previously reported with teriparatide. CONCLUSION The densitometric findings in the context of prolonged PTH elevation and increased bone turnover suggest ronacaleret induces mild hyperparathyroidism. Ronacaleret only modestly increased lumbar spine BMD and decreased BMD at hip sites.
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Plasma osteopontin increases after bariatric surgery and correlates with markers of bone turnover but not with insulin resistance.
Riedl, M, Vila, G, Maier, C, Handisurya, A, Shakeri-Manesch, S, Prager, G, Wagner, O, Kautzky-Willer, A, Ludvik, B, Clodi, M, et al
The Journal of clinical endocrinology and metabolism. 2008;(6):2307-12
Abstract
CONTEXT Osteopontin (OPN) is a multifunctional protein involved in bone metabolism, cardiovascular disease, diabetes, and obesity. OPN levels are elevated in the plasma and adipose tissue of obese subjects, and are decreased with diet-induced weight loss. OBJECTIVE We investigated the effect of bariatric surgery on plasma OPN concentrations in morbidly obese patients. SETTING The study was performed at a university hospital. SUBJECTS We investigated 40 obese patients aged 43.1 +/- 1.8 yr, scheduled to undergo bariatric surgery. Roux-en-Y gastric bypass (RYGB) was performed in 30 subjects (27 females, three males), and laparoscopic adjustable gastric banding (LAGB) in 10 subjects (eight females, two males). STUDY DESIGN All patients were studied before and 1 yr (10.3-14.8 months) after the intervention. MAIN OUTCOME MEASURES OPN, leptin, C-reactive protein, insulin, the homeostatic model assessment insulin resistance index, calcium, 25-hydroxyvitamin D, C telopeptide, and osteocalcin were determined. RESULTS Both bariatric procedures significantly reduced body weight, body mass index, insulin, leptin, and C-reactive protein 1 yr after surgery. Plasma OPN increased from 31.4 +/- 3.8 to 52.8 +/- 3.7 ng/ml after RYGB (P < 0.001) and from 29.8 +/- 6.9 to 46.4 +/- 10.6 ng/ml after LAGB (P = 0.042). Preoperative OPN correlated with age, insulin, the homeostatic model assessment insulin resistance index, and postoperative OPN. Postoperative OPN correlated with C telopeptide and osteocalcin. CONCLUSIONS One year after RYGB and LAGB, plasma OPN levels significantly increased and correlated with biomarkers of bone turnover. Unlike other proinflammatory cytokines, OPN does not normalize but increases further after bariatric surgery.
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Safety and efficacy of teriparatide in elderly women with established osteoporosis: bone anabolic therapy from a geriatric perspective.
Boonen, S, Marin, F, Mellstrom, D, Xie, L, Desaiah, D, Krege, JH, Rosen, CJ
Journal of the American Geriatrics Society. 2006;(5):782-9
Abstract
OBJECTIVES To assess the safety and efficacy of teriparatide in patients aged 75 and older and compare these findings with those of women younger than 75 using data from the Fracture Prevention Trial (FPT). DESIGN The FPT was a randomized, multicenter, double-blind, placebo-controlled study. SETTING The FPT multicenter international study. PARTICIPANTS Postmenopausal women aged 42 to 86 were randomized to placebo (N=544) or teriparatide 20 mug (N=541) by daily self-injection for a median of 19 months. Patients received daily oral supplements of 1,000 mg calcium and 400 to 1,200 IU vitamin D. For this analysis, subgroups were defined according to patient age younger than 75 (N=841) and 75 and older (N=244). MEASUREMENTS The effects of teriparatide on bone mineral density (BMD) of the lumbar spine and femoral neck; the incidence of new vertebral and new nonvertebral fragility fractures; bone turnover markers, including bone-specific alkaline phosphatase; and urinary deoxypyridinoline corrected for creatinine clearance, as well as the safety of teriparatide, were investigated. RESULTS There were no significant treatment-by-age interactions for the bone turnover markers, femoral neck BMD, vertebral fractures, nonvertebral fragility fractures, height loss, hyperuricemia, or hypercalcemia. A significant treatment-by-age interaction for lumbar spine BMD (P=.08) was due to an increase in BMD observed in the placebo group aged 75 and older. There were no treatment-by-age interactions for important treatment-emergent adverse events (TEAEs), including back pain, nausea, leg cramps, and dizziness. The most important TEAEs in women aged 80 and older (23 patients from the placebo group and 25 patients from the teriparatide group) were also reviewed; no unexpected TEAEs were found in the patients treated with teriparatide. These results indicate that the clinical effects of teriparatide were consistent in the older and younger women. CONCLUSION Age does not affect the safety and efficacy of teriparatide in postmenopausal women with osteoporosis.
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Effects of an oral contraceptive containing drospirenone on bone turnover and bone mineral density.
Nappi, C, Di Spiezio Sardo, A, Greco, E, Tommaselli, GA, Giordano, E, Guida, M
Obstetrics and gynecology. 2005;(1):53-60
Abstract
OBJECTIVE To compare the effects of a new 21-day combined oral contraceptive containing 30 microg ethinyl/estradiol plus 3 mg drospirenone with a 21-day preparation containing 30 microg ethinyl/estradiol plus 75 microg gestodene on bone turnover and bone mineral density in young fertile women. METHODS A randomized, controlled trial was conducted with healthy fertile women treated with 30 microg ethinyl/estradiol plus 3 mg drospirenone (group A; n = 24), 30 microg ethinyl/estradiol plus 75 microg gestodene (group B; n = 24) and healthy controls (group C, n = 23). At 3, 6, 9, and 12 months of the study, serum and urinary calcium, osteocalcin, urinary pyridinoline, and deoxypyridinoline were measured. At baseline and after 12 months, lumbar bone mineral density was determined by dual-energy X-ray absorptiometry. RESULTS In groups A and B, urinary pyridinoline and deoxypyridinoline at 6, 9, and 12 months were significantly reduced in comparison with basal values and group C (P < .05). Pyridinoline and deoxypyridinoline levels were lower in group A than in group B throughout the study, but not significantly. In group A serum calcium levels were significantly increased after 6 months. At 12 months, no significant difference was detected in lumbar bone mineral density values among the 3 groups and in comparison with basal values. CONCLUSION Both combined oral contraceptives exert a similar positive influence on bone turnover and bone-sparing effect in young postadolescent women.