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Daidzein and genistein have differential effects in decreasing whole body bone mineral density but had no effect on hip and spine density in premenopausal women: A 2-year randomized, double-blind, placebo-controlled study.
Nayeem, F, Chen, NW, Nagamani, M, Anderson, KE, Lu, LW
Nutrition research (New York, N.Y.). 2019;:70-81
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Abstract
Soy isoflavones are potentially beneficial phytoestrogens, but their tissue-selective effects in women are poorly understood. We tested the hypothesis that soy isoflavones affect bone mineral density (BMD), which may be influenced by individual differences in isoflavone metabolism and serum calcium levels. Ninety-nine healthy premenopausal women were randomized to isoflavones (136.6 mg aglycone equivalence) and 98 to placebo for 5 days per week for up to 2 years. BMD, serum calcium, and urinary excretion of daidzein and genistein were measured before and during treatment. In 129 adherent subjects, we found that isoflavone exposure, determined by urinary excretion levels, but not by dose assignment, interacted with serum calcium in affecting whole body BMD, but not hip and spine BMD. The regression coefficient was -0.042 for genistein excretion (GE) and 0.091 for the interaction between GE and serum calcium (all P < .05). Daidzein excretion had similar but marginal effect. Genistein significantly decreased whole body BMD only at low normal serum calcium levels but increased whole body BMD at higher serum calcium levels. Comparing maximum to minimum GE, mean changes in whole body BMD were +0.033 and -0.113 g/cm2 at serum calcium levels of 10 and 8.15 mg/dL, respectively. These associations were not evident by intention-to-treat analysis, which could not model for inter-individual differences in isoflavone metabolism. In summary, soy isoflavones decrease whole body BMD only when serum calcium is low. Isoflavones are dietary substances that may influence calcium homeostasis by releasing calcium from bone while sparing the common fracture risk sites hip and spine.
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Bone mineral density response rates are greater in patients treated with abaloparatide compared with those treated with placebo or teriparatide: Results from the ACTIVE phase 3 trial.
Miller, PD, Hattersley, G, Lau, E, Fitzpatrick, LA, Harris, AG, Williams, GC, Hu, MY, Riis, BJ, Russo, L, Christiansen, C
Bone. 2019;:137-140
Abstract
BACKGROUND Abaloparatide is a 34-amino acid peptide that selectively binds to the RG conformation of the parathyroid hormone receptor type 1. It was developed for the treatment of women with postmenopausal osteoporosis at high risk of fracture. In ACTIVE, an 18-month phase 3 study (NCT01343004), abaloparatide increased bone mineral density (BMD), decreased the risk of vertebral and nonvertebral fractures compared with placebo, and decreased the risk of major osteoporotic fractures compared with placebo and teriparatide. Here, we report a prospective, exploratory BMD responder analysis from ACTIVE. METHODS Proportions of patients experiencing BMD gains from baseline of >0%, >3%, and >6% at the total hip, femoral neck, and lumbar spine at 6, 12, and 18 months of treatment were compared among the placebo, abaloparatide, and teriparatide groups in ACTIVE. Responders were defined prospectively as patients experiencing BMD gains at all 3 anatomic sites. RESULTS At months 6, 12, and 18, there were significantly more >3% BMD responders in the abaloparatide group compared with placebo and teriparatide: month 6, 19.1% vs 0.9% for placebo and 6.5% for teriparatide; month 12, 33.2% vs 1.5% and 19.8%; month 18, 44.5% vs 1.9% and 32.0% (P < 0.001 for all comparisons of abaloparatide to placebo and to teriparatide). Findings were similar for the >0% and >6% responder thresholds. CONCLUSIONS In postmenopausal women with osteoporosis, a significantly greater proportion of patients treated with abaloparatide experienced increases in BMD than did those treated with placebo or teriparatide.
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Effect of a hypocaloric, nutritionally complete, higher-protein meal plan on bone density and quality in older adults with obesity: a randomized trial.
Weaver, AA, Houston, DK, Shapses, SA, Lyles, MF, Henderson, RM, Beavers, DP, Baker, AC, Beavers, KM
The American journal of clinical nutrition. 2019;(2):478-486
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Abstract
BACKGROUND Dietary protein and micronutrients are important to the maintenance of bone health and may be an effective countermeasure to weight-loss-associated bone loss. OBJECTIVES We aimed to determine the effect of a 6-mo hypocaloric, nutritionally complete, higher-protein meal plan on change in bone density and quality as compared with weight stability in older adults using a randomized post-test design. We hypothesized that participants randomly assigned to this meal plan would maintain similar bone density and quality to weight-stable controls, despite significant reductions in body mass. METHODS Ninety-six older adults (aged 70.3 ± 3.7 y, 74% women, 27% African American) with obesity [body mass index (kg/m2): 35.4 ± 3.3] were randomly assigned to a 6-mo hypocaloric, nutritionally complete, higher-protein meal plan targeting ≥1.0 g protein · kg body weight-1 · d-1 [weight-loss (WL) group; n = 47] or to a weight-stability (WS) group targeting 0.8 g protein · kg body weight-1 · d-1, the current Recommended Dietary Allowance (n = 49). The primary outcome was total hip bone mineral density (BMD), with femoral neck BMD, lumbar spine BMD, and lumbar spine trabecular bone score (TBS) as secondary outcomes, all assessed at baseline and 3 and 6 mo with dual-energy X-ray absorptiometry. RESULTS Baseline total hip, femoral neck, and lumbar spine BMDs were 1.016 ± 0.160, 0.941 ± 0.142, and 1.287 ± 0.246 g/cm2, respectively; lumbar TBS was 1.398 ± 0.109. Despite significant weight loss achieved in the WL group (6.6 ± 0.4 kg; 8.6% ± 0.4% of baseline weight), 6-mo regional BMD estimates were similar to those in the WS group (all P > 0.05). Lumbar spine TBS significantly increased at 6 mo in the WL group (mean: 1.421; 95% CI: 1.401, 1.441) compared with the WS group (1.390: 95% CI: 1.370, 1.409; P = 0.02). CONCLUSIONS Older adults following a hypocaloric, nutritionally complete, higher-protein meal plan maintained similar bone density and quality to weight-stable controls. Our data suggest that adherence to this diet does not produce loss of hip and spine bone density in older adults and may improve bone quality. This trial was registered at clinicaltrials.gov as NCT02730988.
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Interventions for Improving Bone Mineral Density and Reducing Fracture Risk in Osteogenesis Imperfecta: A Mixed Treatment Comparison Network Meta-analysis of Randomized Controlled Clinical Trials.
Sridharan, K, Sivaramakrishnan, G
Current clinical pharmacology. 2018;(3):190-198
Abstract
BACKGROUND Osteogenesis imperfecta is a rare metabolic disorder associated with reduced mineralization of bone and corresponds to increased fracture risk. We carried out the present network meta-analysis comparing all the medical interventions for osteogenesis imperfecta. METHOD Electronic databases were searched for randomized controlled clinical trials evaluating the use of drugs in patients with osteogenesis imperfecta. Percent change in BMD was the primary and fracture risk reduction and adverse events were the secondary outcome measures. The weighted mean difference was the pooled estimate for primary outcome and odds ratio with 95% confidence interval for the secondary outcome measures. Direct and mixed treatment comparisons between the interventions were carried out by inverse heterogeneity model. Sub-group analyses were carried out on children, adults and within bisphosphonate groups. The trial sequential analysis was carried out for the comparison of oral bisphosphonates with placebo. RESULTS A total of 16 studies were included evaluating oral and intravenous bisphosphonates, teriparatide, anti-sclerostin antibody, high dose vitamin D and recombinant growth hormone (rGH) combined with intravenous bisphosphonates. Oral bisphosphonates and teriparatide were observed with a statistically significant increase in BMD compared to placebo. Also, only oral bisphosphonates were associated with significant reduction in the fracture risk but when the alpha error was adjusted for the information accrued till date as well as when the results of a trial were excluded, no significant difference was observed. Either low or very low quality was observed for pooled estimates of the key comparisons. CONCLUSION Oral bisphosphonates and teriparatide significantly increase BMD but are not associated with fracture risk reduction. Of the available interventions, oral bisphosphonates could perform better than others in osteogenesis imperfecta. This evidence should be considered preliminary and may change with future head-to-head clinical trials.
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Changes in blood and urinary cadmium levels and bone mineral density according to osteoporosis medication in individuals with an increased cadmium body burden.
Eom, SY, Yim, DH, Hong, SM, Kim, YD, Kim, H, Choi, BS, Park, JD, Park, CH, Kim, GB, Yu, SD
Human & experimental toxicology. 2018;(4):350-357
Abstract
The aim of this study was to assess changes in bone mineral density (BMD) and cadmium (Cd) levels in blood and urine in individuals living in a Cd-contaminated area according to the type of osteoporosis medication over a three-year period. This follow-up study included 204 residents living in the vicinity of a closed copper refinery, who had been found to have elevated urinary or blood Cd levels. Cd levels in the blood and urine, as well as BMD, were measured every 6 months. After the first BMD measurement, individuals were prescribed antiresorptives such as alendronate or vitamin D and calcium, according to their BMD. Subjects were classified according to the type of medicine provided over the previous 6 months. General linear models controlling for other factors were used to evaluate the effects of each type of medication on the participants' Cd levels and BMD. Spinal BMD showed a significant increase in the antiresorptive group compared to the nontreatment group. Significant decreases in blood Cd levels were found in the vitamin D and calcium group, in comparison to the nontreatment group, as well as a marginally significant decrease in the antiresorptive group. The vitamin D and calcium group showed a significantly greater decrease in urinary Cd levels than the nontreatment group. In contrast, antiresorptive medication was found to have a negative effect on urinary Cd excretion. These results suggest that vitamin D and calcium treatment for osteoporosis lowers blood Cd levels more effectively and improves urinary Cd excretion.
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Effect of testosterone treatment on bone remodelling markers and mineral density in obese dieting men in a randomized clinical trial.
Ng Tang Fui, M, Hoermann, R, Nolan, B, Clarke, M, Zajac, JD, Grossmann, M
Scientific reports. 2018;(1):9099
Abstract
To assess the effect of testosterone treatment on bone remodelling and density in dieting obese men, 100 obese men aged 53 years (interquartile range 47-60) with a total testosterone level <12 nmol/L receiving 10 weeks of a very low energy diet (VLED) followed by 46 weeks of weight maintenance were randomly assigned at baseline to 56 weeks of intramuscular testosterone undecanoate (n = 49, cases) or matching placebo (n = 51, controls). Pre-specified outcomes were between-group differences (mean adjusted difference, MAD) in serum c-telopeptide (CTx), N-terminal propeptide of type 1 procollagen (P1NP) and bone mineral density (BMD). At trial end, CTx was significantly reduced in men receiving testosterone compared to placebo, MAD -66 ng/L (95% CI -113, -18), p = 0.018, and this was apparent already after the 10 week VLED phase, MAD -63 ng/L (95% CI -108, -18), p = 0.018. P1NP was marginally increased after VLED, MAD +4.2 ug/L (95% CI -0.01, +8.4), p = 0.05 but lower at study end, MAD -5.6 ug/L (95% CI -10.1, -1.1), p = 0.03. No significant changes in sclerostin, lumbar spine BMD or femoral BMD were seen. We conclude that in obese men with low testosterone levels undergoing weight loss, bone remodelling markers are modulated in a way that may have favourable effects on bone mass.
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A systematic review and meta-analysis of the effects of isoflavone formulations against estrogen-deficient bone resorption in peri- and postmenopausal women.
Lambert, MNT, Hu, LM, Jeppesen, PB
The American journal of clinical nutrition. 2017;(3):801-811
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Abstract
Background: Age-related estrogen deficiency leads to accelerated bone resorption. There is evidence that, through selective estrogen receptor modulation, isoflavones may exert beneficial effects against estrogen-deficient bone loss. Isoflavone aglycones show higher bioavailability than their glycosidic counterparts and thus may have greater potency.Objective: To summarize evidence, we executed a systematic review and meta-analysis examining isoflavone therapies and bone mineral density (BMD) loss in peri- and postmenopausal women.Design: We systematically searched EMBASE and PubMed for randomized controlled trials (RCTs) evaluating isoflavone therapies for treating BMD loss at the lumbar spine and femoral neck in estrogen-deficient women. Separate meta-analyses were carried out with the use of random-effects models for the lumbar spine and femoral neck for all studies providing isoflavones as aglycones.Results: Twenty-six RCTs (n = 2652) were included in the meta-analysis. At the lumbar spine, isoflavone treatment was associated with a significantly (P < 0.00001) higher weighted mean difference (WMD) of BMD change of 0.01 (95% CI: 0.01, 0.02) than the control. For the femoral neck (18 RCTs, n = 1604), isoflavone treatment showed a significantly (P < 0.01) higher WMD of BMD change of 0.01 (95% CI: 0.00, 0.02) compared with the control. When isolating studies that provide isoflavone aglycones in their treatment arm, the average effect was further significantly increased at the spine (5 RCTs, n = 682) to 0.04 (P < 0.00001; 95% CI: 0.02, 0.05) and femoral neck (4 RCTs, n = 524) to 0.03 (P < 0.05; 95% CI: 0.00, 0.06) compared with the control. This protective effect against bone loss disappeared when only studies with formulations comprising predominantly isoflavone glycosides were included.Conclusions: Isoflavone treatments exert a moderately beneficial effect against estrogen-deficient bone loss in women. The effect appears dependent on whether isoflavone treatments are in aglycone form; we conclude that beneficial effects against bone loss may be enhanced for isoflavone aglycones.
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Periprosthetic femoral bone loss in total hip arthroplasty: systematic analysis of the effect of stem design.
Knutsen, AR, Lau, N, Longjohn, DB, Ebramzadeh, E, Sangiorgio, SN
Hip international : the journal of clinical and experimental research on hip pathology and therapy. 2017;(1):26-34
Abstract
INTRODUCTION Periprosthetic bone loss may lead to major complications in total hip arthroplasty (THA), including loosening, migration, and even fracture. This study analysed the influence of femoral implant designs on periprosthetic bone mineral density (BMD) after THA. METHODS The results of all previous published studies reporting periprosthetic femoral BMD following THA were compiled. Using these results, we compared percent changes in bone loss as a function of: femoral stem fixation, material, and geometry. RESULTS The greatest bone loss was in the calcar region (Gruen Zone 7). Overall, cemented stems had more bone loss distally than noncemented stems, while noncemented stems had more proximal bone loss than cemented stems. Within noncemented stems, cobalt-chromium (CoCr) stems had nearly double the proximal bone loss compared to titanium (Ti) alloy stems. Finally, within noncemented titanium alloy group, straight stems had less bone loss than anatomical, tapered, and press-fit designs. DISCUSSION The findings from the present study quantified percent changes in periprosthetic BMD as a function of fixation method, alloy, and stem design. While no one stem type was identified as ideal, we now have a clearer understanding of the influence of stem design on load transfer to the surrounding bone.
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A Comparative Study of Intravenous Injection Form and Oral Jelly Form of Alendronate Sodium Hydrate for Bone Mineral Disorder after Gastrectomy.
Kunisaki, C, Tanaka, Y, Kosaka, T, Miyamoto, H, Sato, S, Suematsu, H, Yukawa, N, Sato, K, Izumisawa, Y, Akiyama, H, et al
Digestion. 2017;(2):162-171
Abstract
BACKGROUND/AIMS: Osteoporosis is found to have high prevalence after gastrectomy and therefore, it is important to prevent this condition by means of effective medication, such as alendronate sodium hydrate. METHODS A total number of 48 gastric cancer patients diagnosed with osteoporosis after R0 gastrectomy was registered in this study between December 2013 and August 2014. Twenty-three patients received intravenous (i.v.) alendronate sodium hydrate and 25 patients received the drug in an oral jelly form. Serological and urinary examinations related to bone metabolism and bone mineral density (BMD) were performed periodically and the results obtained from the 2 groups were compared. RESULTS BMD increased, serum levels of bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase-5b, and the urine level of urine N-terminal telopeptide decreased with time in both groups. However, the serum Ca level did not change. Two-way analysis of variance revealed no significant differences in these factors between the 2 groups. CONCLUSION It is essential to prevent both forms of osteoporosis by using alendronate sodium hydrate after gastrectomy for gastric cancer. A prospective, randomized, controlled trial in many patients following long duration should be conducted to clarify the benefits of i.v. alendronate sodium hydrate.
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Clinical Inquiries: Does vitamin D without calcium reduce fracture risk?
Daly, S, Allison, C, Nashelsky, J
The Journal of family practice. 2016;(12):933-934
Abstract
Supplemental vitamin D without calcium--in doses averaging as much as 800 IU per day--doesn't reduce the risk of hip, vertebral, or nonvertebral fractures in postmenopausal women and older men.