scholarly journals Low-Dose Zoledronate in Osteopenic Postmenopausal Women: A Randomized Controlled Trial

2012 ◽  
Vol 97 (1) ◽  
pp. 286-292 ◽  
Author(s):  
Andrew Grey ◽  
Mark Bolland ◽  
Sumwai Wong ◽  
Anne Horne ◽  
Greg Gamble ◽  
...  
Keyword(s):  
Placebo Group ◽  
Confidence Interval ◽  
Bone Turnover ◽  
Postmenopausal Women ◽  
Type I Collagen ◽  
Controlled Trial ◽  
Type I ◽  
Mineral Density ◽  
Double Blind ◽  
Skeletal Effects

Context: Annual iv administration of 5 mg zoledronate decreases fracture risk. The skeletal effects of annual treatment with doses of zoledronate under 4 mg have not been assessed. Objective: Our objective was to determine the skeletal effects of single doses of zoledronate of 5 mg or less. Design, Setting, and Participants: This was a double-blind, randomized, placebo-controlled trial over 1 yr at an academic research center in 180 postmenopausal women with osteopenia. Intervention: Intervention was a single baseline administration of iv zoledronate in doses of 1, 2.5, or 5 mg, or placebo. Main Outcome Measures: The primary endpoint was change in bone mineral density (BMD) at the lumbar spine. Secondary endpoints were change in BMD at the proximal femur and total body and changes in biochemical markers of bone turnover. Results: After 12 months, change in spine BMD was greater in each of the zoledronate groups than in the placebo group [mean (95% confidence interval) difference vs. placebo was 3.5% (2.2–4.8%) for 1 mg, 4.0% (2.7–5.3%) for 2.5 mg, and 3.6% (2.3–4.9%) for 5 mg zoledronate, P < 0.001 for each dose]. Change in BMD at the total hip was greater in each of the zoledronate groups than the placebo group [mean (95% confidence interval) difference vs. placebo was 2.7% (1.9–3.5%) for 1 mg, 3.6% (2.8–4.4%) for 2.5 mg, and 3.6% (2.8–4.4%) for 5 mg zoledronate, P < 0.001 for each dose]. Each of the bone turnover markers, β-C-terminal telopeptide of type I collagen and procollagen type I N-terminal propeptide, was lower by at least 40% in each of the zoledronate groups than the placebo group throughout the trial (P < 0.001 vs. placebo for each marker for each dose). There was evidence for a dose-dependent effect of zoledronate on each of the markers (P for trend <0.001). Conclusion: Annual administration of doses of iv zoledronate lower than 5 mg produces substantial antiresorptive effects. Trials assessing the antifracture efficacy of low doses of zoledronate are justified.

scholarly journals Genetic polymorphisms and their influence on therapeutic response to alendronate-a pilot study

2019 ◽  
Vol 10 (Vol.10, No.3) ◽  
pp. 243-251
Author(s):  
Alina Deniza CIUBEAN ◽  
Laszlo IRSAY ◽  
Rodica Ana UNGUR ◽  
Viorela Mihaela CIORTEA ◽  
Ileana Monica BORDA ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Lumbar Spine ◽  
Bone Turnover ◽  
Postmenopausal Women ◽  
Bone Mineral ◽  
Bone Turnover Markers ◽  
Type I Collagen ◽  
Type I ◽  
Mineral Density ◽  
Turnover Markers

Introduction: Osteoporosis has a strong genetic contribution, and several genes have been shown to influence bone mineral density. Variants in the human genome are considered important causes of differences in drug responses observed in clinical practice. In terms of bone mineral density, about 26–53% of patients do not respond to amino-bisphosphonate therapies, of which alendronate is the most widely used. Material and method: The current study is prospective, observational, analytical, longitudinal and cohort type. It included 25 postmenopausal women treated with alendronate for 1 year. Bone mineral density at lumbar spine and proximal femur was measured and bone turnover markers (C-terminal telopeptide of type I collagen and procollagen 1N-terminal propeptide) were evaluated at 0 and 12 months of treatment. Six single nucleotide polymorphisms in osteoporosis-candidate genes were genotyped (FDPS rs2297480, LRP5 rs3736228, SOST rs1234612, VKORC1 rs9934438, GGPS1 rs10925503 and RANKL rs2277439). Treatment response was evaluated by percentage changes in bone mineral density and bone turnover markers. Results: The heterozygous CT of FDPS rs2297480 showed lower increases in BMD values in the lumbar spine region and the homozygous CC of the GGPS1 rs10925503 showed lower increases in terms of BMD at the total hip region. No association was found for LRP5 rs3736228, SOST rs1234612, VKORC1 rs9934438 and RANKL rs2277439. Conclusions: Romanian postmenopausal women with osteoporosis carrying the CT genotype of FDPS rs2297480 or the CC genotype of GGPS1 rs10925503 could have an unsatisfactory response to alendronate treatment. Key words: osteoporosis; genetic polymorphism; alendronate; bone mineral density; bone turnover markers,

Alpha-Ketoglutarate Decreases Serum Levels of C-terminal Cross-Linking Telopeptide of Type I Collagen (CTX) in Postmenopausal Women with Osteopenia: Six-Month Study

2007 ◽  
Vol 77 (2) ◽  
pp. 89-97 ◽  
Author(s):  
Filip ◽  
Pierzynowski ◽  
Lindegard ◽  
Wernerman ◽  
Haratym-Maj ◽  
...  
Keyword(s):  
Lumbar Spine ◽  
Postmenopausal Women ◽  
Type I Collagen ◽  
Skeletal Development ◽  
Serum Levels ◽  
Study Groups ◽  
Type I ◽  
Mineral Density ◽  
Double Blind ◽  
Beneficial Effects

Several studies have shown that α-ketoglutaric acid (AKG) increases serum levels of proline and has beneficial effects on skeletal development. We studied the effect of α-ketoglutaric (AKG) acid calcium salt (6 g AKG and 1.68 Ca/day) or calcium alone (1.68 Ca/day) on serum C-terminal cross-linked telopeptide of type I collagen (CTX) and osteocalcin (OC), as well as on lumbar spine bone mineral density (BMD) in a randomized, parallel group, double-blind, 6-month study conducted on 76 postmenopausal women with osteopenia. The maximum decrease of the mean CTX level in the AKG-Ca group was observed after 24 weeks (37.0%, p = 0.006). The differences in CTX between study groups were statistically significant after 12 and 24 weeks. The OC serum level was not affected by treatments. The BMD of the AKG-Ca group increased by 1.6% from baseline; however, the difference between treatment groups was estimated as 0.9% (non-significant). This study suggests the potential usefulness of AKG-Ca in osteopenic postmenopausal women. AKG-Ca induced beneficial changes in serum CTX, which was consistent with preserving the bone mass in the lumbar spine; however, the long-term effect needs to be further investigated.

Effects of Omega-3 Polyunsaturated Fatty Acid Supplementation on Bone Turnover in Older Women

2014 ◽  
Vol 84 (3-4) ◽  
pp. 0124-0132 ◽  
Author(s):  
Hongli Dong ◽  
Heather Hutchins-Wiese ◽  
Alison Kleppinger ◽  
Kristen Annis ◽  
Enrico Liva ◽  
...  
Keyword(s):  
Placebo Group ◽  
Fatty Acid ◽  
Bone Turnover ◽  
Postmenopausal Women ◽  
Controlled Trial ◽  
Omega 3 ◽  
Double Blind ◽  
Pufa Supplementation ◽  
Bone Specific Alkaline Phosphatase ◽  
Turnover Markers

Animal and human studies indicate that omega (n)-3 polyunsaturated fatty acids (PUFA) can influence bone health. We conducted a randomized, double-blind, placebo-controlled trial of the effects of n-3 long chain (LC) PUFA supplementation (N-3 LCPUFA) on red blood cell (RBC) fatty acid levels and bone turnover markers in older postmenopausal women. One hundred and twenty-six postmenopausal women (mean age 75 ± 7 years) were treated with n-3 LCPUFA (1.2 g eicosapentaenoic acid [EPA]/docosahexaenoic acid [DHA]/day, n = 85) or placebo (olive oil, n = 41) for 6 months. All women received 315 mg calcium citrate and 1000 IU cholecalciferol. RBC DHA (weight %) increased in the n-3 LCPUFA group, compared to no change in the placebo group (P < 0.001). The ratio of DHA+EPA:arachidonic acid (AA) increased by 42 % in the n-3 LCPUFA group and by 5 % in the placebo group (P < 0.001). Bone-specific alkaline phosphatase and osteocalcin decreased in the n-3 LCPUFA group (P < 0.05) with no between-group difference. Short-term n-3 LCPUFA supplementation increased RBC concentrations of DHA and n-3:n-6 ratios. Bone turnover decreased with n-3 LCPUF, but not statistically compared to placebo. The results point to the need for investigations with greater dosages of n-3 LCPUFA for a longer duration to understand the contribution to bone metabolism in postmenopausal women.

Su.106. Clinical Effects of Intraarticular Injection of Polymerized-Type I Collagen: a Double-Blind, Randomized, Placebo-Controlled Trial

2006 ◽  
Vol 119 ◽  
pp. S196
Author(s):  
Janette Furuzawa-Carballeda ◽  
Andres Agualimpia-Janning ◽  
Olga Munoz-Chable ◽  
Salvador Macias-Hernandez
Keyword(s):  
Type I Collagen ◽  
Controlled Trial ◽  
Intraarticular Injection ◽  
Type I ◽  
Clinical Effects ◽  
Double Blind

scholarly journals Coated-tube radioimmunoassay for C-telopeptides of type I collagen to assess bone resorption

1996 ◽  
Vol 42 (10) ◽  
pp. 1639-1644 ◽  
Author(s):  
M Bonde ◽  
C Fledelius ◽  
P Qvist ◽  
C Christiansen
Keyword(s):  
Bone Resorption ◽  
Postmenopausal Women ◽  
Type I Collagen ◽  
Premenopausal Women ◽  
Type I ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Analytical Recovery ◽  
Controlled Clinical Study ◽  
Different Doses

Abstract We present a coated-tube RIA that is useful for assessment of bone resorption. The assay uses a monoclonal antibody raised against a linear 8-amino-acid sequence (EKAHDGGR) derived from the C-telopeptides of type I collagen. Within-run and total CVs were 4.4% and 5.3-6.2%, respectively, at concentrations of 1-7 mg/L (n = 4-20). Analytical recovery was 98% +/- 8% and dilution 97% +/- 7%. Values obtained in a group of 36 premenopausal women were 227 +/- 89.6 mg/mol creatinine. In a group of 141 postmenopausal women, the values obtained were 429 +/- 225 mg/mol creatinine, a highly significant increase of 89% (P &lt;0.001) over the premenopausal value. In a double-blind placebo-controlled clinical study of these postmenopausal women receiving five different doses of a bisphosphonate, a significant decrease of RIA-measured C-telopeptide values was seen in all bisphosphonate-treated groups, after just 3 months. Values in urine samples from postmenopausal women assayed with the RIA (gamma) and the CrossLaps(TM) ELISA (x) agreed well: slope = 0.98 (95% confidence interval, 0.94-1.01), intercept = 0.34 (0.25-0.43) mg/L, and Sylx = 0.93 mg/L (n = 678). We conclude that this RIA represents a valuable tool for assessing bone resorption.

Cinnarizine and sodium valproate as the preventive agents of pediatric migraine: A randomized double-blind placebo-controlled trial

Cephalalgia ◽  
2019 ◽  
Vol 40 (7) ◽  
pp. 665-674
Author(s):  
Man Amanat ◽  
Mansoureh Togha ◽  
Elmira Agah ◽  
Mahtab Ramezani ◽  
Ali Reza Tavasoli ◽  
...  
Keyword(s):  
Placebo Group ◽  
Adverse Effects ◽  
Confidence Interval ◽  
Children And Adolescents ◽  
Sodium Valproate ◽  
Medical Center ◽  
Controlled Trial ◽  
Migraine Prophylaxis ◽  
Double Blind ◽  
Double Blind Placebo

Background Few migraine preventive agents have been assessed in a pediatric population. We evaluated the safety and efficacy of cinnarizine and sodium valproate for migraine prophylaxis in children and adolescents. Methods We carried out a randomized double-blind placebo-controlled trial in the Children’s Medical Center and Sina hospital, Tehran, Iran. Eligible participants were randomly assigned in 1:1:1 ratio via interactive web response system to receive either cinnarizine, sodium valproate, or placebo. The primary endpoints were the mean change in frequency and intensity of migraine attacks from baseline to the last 4 weeks of trial. The secondary endpoint was the efficacy of each drug in the prevention of migraine. The drug was considered effective if it decreased migraine frequency by more than 50% in the double-blind phase compared with the baseline. Safety endpoint was adverse effects that were reported by children or their parents. Results A total of 158 children participated. The frequency of migraine attacks significantly reduced compared to baseline in cinnarizine (difference: −8.0; 95% confidence interval (CI): −9.3 to −6.6), sodium valproate (difference: −8.3; 95% confidence interval: −9.3 to −7.2), and placebo (difference: −4.4; 95% confidence interval: −5.4 to −3.4) arms. The decrease was statistically greater in cinnarizine (difference: −3.6; 95% confidence interval: −5.5 to −1.6) and sodium valproate (difference: −3.9; 95% confidence interval: −5.8 to −1.9) arms, compared to placebo group. Children in all groups had significant reduction in intensity of episodes compared to baseline (cinnarizine: −4.6; 95% confidence interval: −5.2 to −4.0; sodium valproate: −4.0; 95% confidence interval: −4.8 to −3.3; placebo: −2.6; 95% confidence interval: −3.4 to −1.8). The decrease was statistically greater in cinnarizine (difference: −2.0; 95% confidence interval: −3.2 to −0.8) and sodium valproate (difference: −1.5; 95% confidence interval: −2.7 to −0.3) arms, compared to the placebo group. Seventy-one percent of individuals in the cinnarizine group, 66% of cases in the sodium valproate group, and 42% of people in the placebo arm reported more than 50% reduction in episodes at the end of the trial. The odds ratio for >50% responder rate was 3.5 (98.3% confidence interval: 1.3 to 9.3) for cinnarizine versus placebo and 2.7 (98.3% confidence interval: 1.0 to 6.9) for sodium valproate versus placebo. Nine individuals reported adverse effects (three in cinnarizine, five in sodium valproate, and one in the placebo group) and one case in the sodium valproate group discontinued the therapy due to severe sedation. Conclusion Cinnarizine and sodium valproate could be useful in migraine prophylaxis in children and adolescents. Trial registration: IRCT201206306907N4.

scholarly journals Exercise Mitigates Bone Loss in Women With Severe Obesity After Roux-en-Y Gastric Bypass: A Randomized Controlled Trial

2019 ◽  
Vol 104 (10) ◽  
pp. 4639-4650 ◽  
Author(s):  
Igor H Murai ◽  
Hamilton Roschel ◽  
Wagner S Dantas ◽  
Saulo Gil ◽  
Carlos Merege-Filho ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Bone Loss ◽  
Bone Turnover ◽  
Distal Radius ◽  
Biochemical Markers ◽  
Severe Obesity ◽  
Controlled Trial ◽  
Type I ◽  
Mineral Density ◽  
Randomized Controlled

Abstract Context Bone loss after bariatric surgery potentially could be mitigated by exercise. Objective To investigate the role of exercise training (ET) in attenuating bariatric surgery–induced bone loss. Design Randomized, controlled trial. Setting Referral center for bariatric surgery. Patients Seventy women with severe obesity, aged 25 to 55 years, who underwent Roux-en-Y gastric bypass (RYGB). Intervention Supervised, 6-month, ET program after RYGB vs. standard of care (RYGB only). Outcomes Areal bone mineral density (aBMD) was the primary outcome. Bone microarchitecture, bone turnover, and biochemical markers were secondary outcomes. Results Surgery significantly decreased femoral neck, total hip, distal radius, and whole body aBMD (P < 0.001); and increased bone turnover markers, including collagen type I C-telopeptide (CTX), procollagen type I N-propeptide (P1NP), sclerostin, and osteopontin (P < 0.05). Compared with RYGB only, exercise mitigated the percent loss of aBMD at femoral neck [estimated mean difference (EMD), −2.91%; P = 0.007;], total hip (EMD, −2.26%; P = 0.009), distal radius (EMD, −1.87%; P = 0.038), and cortical volumetric bone mineral density at distal radius (EMD, −2.09%; P = 0.024). Exercise also attenuated CTX (EMD, −0.20 ng/mL; P = 0.002), P1NP (EMD, −17.59 ng/mL; P = 0.024), and sclerostin levels (EMD, −610 pg/mL; P = 0.046) in comparison with RYGB. Exercise did not affect biochemical markers (e.g., 25(OH)D, calcium, intact PTH, phosphorus, and magnesium). Conclusion Exercise mitigated bariatric surgery–induced bone loss, possibly through mechanisms involving suppression in bone turnover and sclerostin. Exercise should be incorporated in postsurgery care to preserve bone mass.

Effects of everolimus (EVE) on disease progression in bone and bone markers (BMs) in patients (pts) with bone metastases (mets).

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 102-102 ◽  
Author(s):  
Lowell L. Hart ◽  
José Baselga ◽  
Hope S. Rugo ◽  
Shinzaburo Noguchi ◽  
Kathleen I. Pritchard ◽  
...  
Keyword(s):  
Bone Turnover ◽  
Type I Collagen ◽  
Bone Lesion ◽  
Phase Iii ◽  
Type I ◽  
Double Blind ◽  
Mtor Inhibition ◽  
Similar Frequency ◽  
Once Daily ◽  
Amino Terminal

102 Background: BOLERO-2, a multinational, double-blind, placebo-controlled, phase III study in postmenopausal women with estrogen-receptor–positive breast cancer (BC) refractory to nonsteroidal aromatase inhibitors (NSAIs), showed significant clinical benefits with the addition of EVE to exemestane (EXE) (Baselga J et al. NEJM2011 Epub). As bone resorption is an important factor in BC mets, it is interesting to study bone-related effects of EVE. In preclinical studies, mTOR inhibition was associated with decreased osteoclast survival and activity. Exploratory analyses in BOLERO-2 evaluated the effects of EVE vs placebo (PBO) on BM levels and BC progression in bone in pts with bone mets at baseline. Methods: Eligible pts were treated with EXE (25 mg once daily) and randomized (2:1) to EVE (10 mg once daily) or PBO. Bone turnover markers (BMs) were exploratory endpoints analyzed at 6 and 12 wks after treatment initiation and included bone-specific alkaline phosphatase, amino-terminal propeptide of type I collagen, and C-terminal cross-linking telopeptide of type I collagen. Progressive disease in bone (PDB) was defined as worsening of a preexisting bone lesion or a new bone lesion. Results: Baseline disease characteristics, including bone mets at baseline (n = 370, 76% EVE vs n = 184, 77% PBO), were well balanced between arms (N = 724), and baseline bisphosphonate use was not (44% EVE vs 55% PBO). At 12.5 mo median follow-up, progression-free survival (primary endpoint), overall response rate, and clinical benefit rate (p < 0.0001, all) were significantly higher with EVE (n = 485) vs PBO (n = 239). BM levels at 6 and 12 wks increased vs baseline with PBO but decreased with EVE. The cumulative incidence rate of BC PBD was lower for EVE vs PBO at day 60 (3.03% vs 6.16%, respectively), and this trend was sustained beyond 6 months. Updated results will be presented. All bone-related adverse events reported were grade 1-2 and occurred with similar frequency in EVE (2.9%)- and PBO (3.8%)-treated patients. Conclusions: Exploratory analyses from BOLERO-2 suggest that adding EVE has beneficial effects on bone turnover and BC progression in bone in pts receiving EXE therapy for NSAI-refractory BC.

scholarly journals Effect of Calcium or 25OH Vitamin D3 Dietary Supplementation on Bone Loss at the Hip in Men and Women over the Age of 60*

2000 ◽  
Vol 85 (9) ◽  
pp. 3011-3019 ◽  
Author(s):  
Munro Peacock ◽  
Guangda Liu ◽  
Mark Carey ◽  
Ronald McClintock ◽  
Walter Ambrosius ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Turnover ◽  
Secondary Hyperparathyroidism ◽  
Vitamin D3 ◽  
Bone Structure ◽  
Controlled Trial ◽  
Drop Out ◽  
Mineral Density ◽  
Serious Adverse Events ◽  
Double Blind

Abstract Dietary supplements that prevent bone loss at the hip and that can be applied safely in the elderly are likely to reduce hip fractures. A daily dietary supplement of 750 mg calcium or 15 μg 25OH vitamin D3 on bone loss at the hip and other sites, bone turnover and calcium-regulating hormones were studied over 4 yr in elderly volunteers using a randomized, double-blind, placebo-controlled trial. Bone mineral density (BMD) was measured by dual x-ray absorptiometry and bone structure by radiographs. Calcium biochemistry and bone turnover markers were measured in blood and urine. The 316 women entering the trial had a mean age of 73.7 yr and the 122 men of 75.9 yr. Baseline median calcium intake was 546 mg/day, and median serum 25OH vitamin D3 was 59 nmol/L. On placebo, loss of BMD at total hip was 2% and femoral medulla expansion was 3% over 4 yr. Calcium reduced bone loss, secondary hyperparathyroidism, and bone turnover. 25OH vitamin D3 was intermediate between placebo and calcium. Fracture rates and drop-out rates were similar among groups, and there were no serious adverse events with either supplement. A calcium supplement of 750 mg/day prevents loss of BMD, reduces femoral medullary expansion, secondary hyperparathyroidism, and high bone turnover. A supplement of 15 μg/day 25OH vitamin D3 is less effective, and because its effects are seen only at low calcium intakes, suggests that its beneficial effect is to reverse calcium insufficiency.

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