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Predictive Power of Bone Turnover Biomarkers to Estimate Bone Mineral Density after Kidney Transplantation with or without Denosumab: A post hoc Analysis of the POSTOP Study.
Heimgartner, N, Graf, N, Frey, D, Saleh, L, Wüthrich, RP, Bonani, M
Kidney & blood pressure research. 2020;(5):758-767
Abstract
BACKGROUND Low bone mineral density (BMD) represents a major risk factor for bone fractures in patients with chronic kidney disease (CKD) as well as after kidney transplantation. However, modalities to solidly predict patients at fracture risk are yet to be defined. Better understanding of bone turnover biomarkers (BTMs) may close this diagnostic gap. This study strives to correlate BTMs to BMD in kidney transplant recipients. METHODS Changes in BTMs - procollagen type I N-terminal propeptide (P1NP), bone-specific alkaline phosphatase (BSAP), β-isomer of the C-terminal telopeptide of type I collagen, and urine deoxypyridinoline/Cr - at the time of transplant and 3 months were correlated to changes in BMD measured by dual-energy X-ray absorptiometry at the time of transplant, 6, and 12 months, respectively. Half of the collective was treated with denosumab twice yearly in addition to the standard treatment with calcium and vitamin D. RESULTS Changes in bone formation markers BSAP and P1NP within 3 months showed a significant negative correlation to changes in BMD at the hip within 6 months in denosumab-naïve patients. This correlation was abrogated by denosumab treatment. CONCLUSIONS Changes in BSAP and P1NP showed promise in short-term prediction of BMD. We suggest further trials expanding on the knowledge of these BTMs with assessment of fracture risk, sequential measurements of BTMs within the first 6 months, and the additional use of computed tomography to assess BMD.
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Bazedoxifene effects on osteoprotegerin, insulin-like growth factor, tumor necrosis factor and bone mineral density.
Ma, Y, Chai, Z, Ren, L, Hu, Q
Cellular and molecular biology (Noisy-le-Grand, France). 2020;(3):109-112
Abstract
UNLABELLED To observe the clinical effect of estrogenic drugs (Bazedoxifene) on bone targeting in the treatment of osteoporosis and explore its mechanism. METHODS 112 patients with postmenopausal osteoporosis who received Bazedoxifene drugs in our hospital from January to December 2018 were collected as a study group, and 56 patients treated with calcium alone were collected as a control group. the risk of adverse events such as bone mineral density, osteoprotegerin (OPG), insulin-like growth factor (IGF), tumor necrosis factor (TNF-α), and fracture after treatment were analyzed before and after treatment. RESULTS There was no significant difference in the mean lumbar positive position (L2-4) and right femoral neck bone density and OPG, IGF, TNF-α level between the two groups before treatment (P>0.05). The total effective rate of clinical treatment in the study group was 88.39%, the control group was 23.21%, the difference between the two groups was statistically significant (P˂0.05). After treatment, the mean lumbar positive position (L2-4) and the right femoral neck bone density and OPG, IGF in the study group were higher than those in the control group, lower than those in the control group (P<0.05). the occurrence of adverse events such as fracture, spinal deformation and fatigue in the study group after 12 months of treatment was significantly lower than that in the control group (P<0.05), but there was no significant difference in the occurrence of hot flashes and venous thromboembolism between the two groups (P>0.05). CONCLUSION Bazedoxifene is an effective drug for the treatment of postmenopausal osteoporosis. It can not only prevent the rapid loss of bone mass, effectively relieve the symptoms of menopause, but also improve bone density and reduce the risk of fracture.
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Exposure-Safety Analyses Identify Predictors of Change in Bone Mineral Density and Support Elagolix Labeling for Endometriosis-Associated Pain.
Abbas Suleiman, A, Nader, A, Winzenborg, I, Beck, D, Polepally, AR, Ng, J, Noertersheuser, P, Mostafa, NM
CPT: pharmacometrics & systems pharmacology. 2020;(11):639-648
Abstract
Elagolix is a novel oral gonadotropin releasing hormone receptor antagonist, that can suppress estradiol in a dose-dependent manner. It is indicated for management of moderate-to-severe pain associated with endometriosis. A population exposure-response model describing the relationship between elagolix exposure and changes in bone mineral density (BMD) was developed using data from four phase III studies in premenopausal women with endometriosis-associated pain. Elagolix pharmacokinetic exposure-dependent changes in BMD were described by an indirect-response maximum effect (Emax ) model through stimulation of bone resorption. African American race, higher body mass index (BMI), and lower type-I collagen C-telopeptide concentrations were significantly associated with higher baseline BMD. Higher BMI was significantly associated with higher bone formation rates. Simulations using the final model demonstrated that elagolix 150 mg q.d. dosing for 24 months is predicted to result in -1.45% (-2.04 to -0.814) decrease from baseline in BMD and were used to support corresponding dosing recommendations in the label.
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Exercise Mode Specificity for Preserving Spine and Hip Bone Mineral Density in Prostate Cancer Patients.
Newton, RU, Galvão, DA, Spry, N, Joseph, D, Chambers, SK, Gardiner, RA, Wall, BA, Bolam, KA, Taaffe, DR
Medicine and science in sports and exercise. 2019;(4):607-614
Abstract
PURPOSE Androgen deprivation therapy (ADT) in men with prostate cancer (PCa) is associated with an array of adverse effects, including reduced bone mineral density (BMD) predisposing patients to increased fracture risk. Our purpose was to examine the effects of targeted exercise modes on BMD in men with PCa undergoing ADT. METHODS Between 2009 and 2012, 154 PCa patients 43-90 yr old on ADT were randomized to exercise targeting the musculoskeletal system (impact loading + resistance training [ImpRes], n = 57) supervised for 12 months, cardiovascular and muscular systems (aerobic + resistance training, n = 50) supervised for 6 months followed by a 6-month home-based program, or delayed aerobic exercise (DelAer, n = 47) received exercise information for 6 months followed by 6 months of supervised aerobic exercise (stationary cycling). End points were lumbar spine, hip and whole-body BMD measured by dual-energy x-ray absorptiometry with secondary end points of lean and fat mass, appendicular skeletal muscle mass, and neuromuscular strength. ANOVA was used to compare the exercise groups with DelAer at 6 and 12 months. RESULTS There was a between-group difference in BMD for ImpRes and DelAer at the spine (6 months, P = 0.039; 12 months, P = 0.035) and femoral neck (6 months, P = 0.050), with decline attenuated in ImpRes (~-1.0% vs ~-2.0%). Compared with DelAer, ImpRes increased appendicular skeletal muscle at 6 months (0.3 kg, P = 0.045) and improved muscle strength at 6 and 12 months (P ≤ 0.012) by 9%-34%. A limitation was inclusion of well-functioning patients. CONCLUSION Combined impact loading and resistance exercise attenuates bone loss at the spine and enhances overall musculoskeletal function in PCa patients undergoing ADT.
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Calcium intake improvement after nutritional intervention in paediatric patients with osteogenesis imperfecta.
Zambrano, MB, Félix, TM, Mello, ED
Journal of human nutrition and dietetics : the official journal of the British Dietetic Association. 2019;(5):619-624
Abstract
BACKGROUND In several bone disorders, adequate calcium intake is a coadjuvant intervention to regular treatment. Osteogenesis imperfecta (OI) is a collagen disorder with a range of symptoms, ranging from fractures to minimum trauma, and it is typically treated with bisphosphonates. In the present study, we evaluate the impact of a nutritional intervention (NI) on dietary calcium intake and bone mineral density (BMD) in paediatric patients with OI. METHODS A nonrandomised clinical trial was designed with a NI. Dietary calcium intake, anthropometry and clinical features were assessed at baseline, including anthropometry, basal metabolic rate (BMR), BMD. In addition, a food guidance form was developed and sent to patients by mail. After 12 months, clinical features of patients were reassessed and compared with the baseline data. RESULTS Fifty-two children and adolescents were enrolled. Significant increases in total calcium intake (mg day-1 ), percentage of adequate calcium intake (%) and number of cups of milk ingested were observed after NI. We detected a positive correlation between the variation of BMD and milk consumption in patients treated with bisphosphonate. CONCLUSIONS We observed an increase in calcium intake in patients with OI. This finding demonstrates the importance of nutrition therapy as part of a multidisciplinary treatment approach for bone health.
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Association of Dietary Niacin Intake With Incident Hip Fracture, BMD, and Body Composition: The Cardiovascular Health Study.
Carbone, LD, Bůžková, P, Fink, HA, Raiford, M, Le, B, Isales, CM, Shikany, JM, Coughlin, SS, Robbins, JA
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2019;(4):643-652
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Abstract
Interest in niacin has increased in the setting of reports suggesting that niacin plays a role in diseases of aging. No study to date has examined the association of dietary niacin intake with multiple skeletal health parameters including bone mineral density (BMD), hip fractures, and body composition, and none have included both African American and white men and women. Participants included 5187 men and women ≥65 years from the Cardiovascular Health Study (CHS). Mean daily dietary niacin intake was 32.6 mg, with quartiles 1 through 4 defined as 3.6 to 21.8 mg/day, 21.9 to 30.2 mg/day, 30.3 to 40.9 mg/day, and 41.0 to 102.4 mg/day, respectively. Risk of incident hip fracture per 10 mg increment of daily dietary niacin intake was estimated using proportional hazards models. During a median follow-up of 13 years, 725 participants had an incident hip fracture. In models adjusted for demographic and clinical characteristics and diet, dietary niacin intake was significantly associated with an increased risk of hip fractures (hazard ratio [HR] 1.12; 95% CI, 1.01 to 1.24) with spline models suggesting a U-shaped association. In post hoc analyses, both the lowest (HR 1.31; 95% CI, 1.04 to 1.66) and highest (HR 1.53; 95% CI, 1.20 to 1.95) quartiles of niacin intake were associated with an increased risk of incident hip fracture versus quartiles 2 and 3. There was a trend for a significant inverse association of dietary niacin intake with hip BMD (p = 0.06), but no significant association with total body BMD or any body composition measures. In this cohort of elderly, community-dwelling African American and white men and women, both high and low dietary niacin intakes were associated with a significantly increased risk of subsequent hip fracture, suggesting a possible U-shaped association. By comparison, dietary niacin may have an inverse linear association with hip BMD. © 2018 American Society for Bone and Mineral Research.
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Comparison of the effect of vitamin D on osteoporosis and osteoporotic patients with healthy individuals referred to the Bone Density Measurement Center.
Shahnazari, B, Moghimi, J, Foroutan, M, Mirmohammadkhani, M, Ghorbani, A
Biomolecular concepts. 2019;(1):44-50
Abstract
Objective Osteoporosis is the most common metabolic disease of the bones. Osteoporosis reduces bone density, predisposes a person to fractures, and imposes high costs on societies. Osteoporosis develops from a variety of causes, one of the most significant is vitamin D deficiency. This study investigates the impact of vitamin D on osteoporosis. Materials and Methods In this clinical trial, 400 patients referred to the Bone Density Clinic of Kowsar Hospital in Semnan were selected by convenience sampling method. Bone densitometry tests were carried out using DEXA (x-ray absorptiometry) and serum vitamin D levels were measured by the ELISA method. Subjects with vitamin D deficiency were treated for 8 weeks with (50,000 Vitamin D units per week. At the end of the treatment period, all subjects were evaluated for bone density and the results of both groups were compared. Results 13% of subjects had osteoporosis and 14.2% had osteopenia. 19% of subjects had vitamin D deficiency, 38.8% had insufficient levels of vitamin D, and 42.3% had sufficient vitamin D levels. The level of vitamin D in patients with osteoporosis (5.50 ± 5.5 ng/ml) was less than those with osteopenia (7.83 ± 4.8 ng/ml) and those with normal bone mineral density (23.88 ± 18.42 ng/ml) (P <0.001). The prevalence of osteoporosis in the intervention group after intervention with vitamin D was significantly lower than the control group (32.3 versus 67.7 and P <0.001). Conclusion The prevalence of serum vitamin D deficiency in osteopenic and osteoporotic individuals was higher than in normal subjects, with a significant relationship between age and sex. Thus, treatment with vitamin D improves bone density indices.
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Bone mineral density in virologically suppressed people aged 60 years or older with HIV-1 switching from a regimen containing tenofovir disoproxil fumarate to an elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide single-tablet regimen: a multicentre, open-label, phase 3b, randomised trial.
Maggiolo, F, Rizzardini, G, Raffi, F, Pulido, F, Mateo-Garcia, MG, Molina, JM, Ong, E, Shao, Y, Piontkowsky, D, Das, M, et al
The lancet. HIV. 2019;(10):e655-e666
Abstract
BACKGROUND Tenofovir alafenamide is associated with less renal and bone toxicity than tenofovir disoproxil fumarate and might improve the long-term safety of antiretroviral therapy. We aimed to investigate the effect on bone mineral density of switching from a regimen containing tenofovir disoproxil fumarate to one containing tenofovir alafenamide in participants aged 60 years and older. METHODS We did a prospective, open-label, multicentre, randomised trial in 36 European centres. Participants were virologically suppressed (HIV-1 RNA <50 copies per mL), aged 60 years or older, on a tenofovir disoproxil fumarate-containing regimen and were randomly assigned (2:1) via an interactive web-response system to open-label elvitegravir (150 mg), cobicistat (150 mg), emtricitabine (200 mg), and tenofovir alafenamide (10 mg) daily or continued therapy containing tenofovir disoproxil fumarate (300 mg). Participants were stratified by spine and hip bone mineral density categories. Primary endpoints were change from baseline to week 48 in spine and hip bone mineral density with a null hypothesis of zero between-group difference tested at a significance level of 0·05. This study was registered with ClinicalTrials.gov, NCT02616783. FINDINGS Between Dec 22, 2015, and March 21, 2018, 167 participants were randomly assigned to elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide (n=111 [66%]) or tenofovir disoproxil fumarate (n=56 [34%]). One participant in the elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide group did not receive treatment and was excluded from all analyses. At week 48, the mean percentage change in spine bone mineral density was 2·24% (SD 3·27) in the elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide group and -0·10% (3·39) in the tenofovir disoproxil fumarate group (between-group difference 2·43% [95% CI 1·34-3·52]; p<0·0001), and mean percentage change in hip bone mineral density was 1·33% (2·20) in the elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide group and -0·73% (3·21) in the tenofovir disoproxil fumarate group (difference 2·04% [1·17-2·90]; p<0·0001). The most common adverse events were nasopharyngitis (12 [11%]), back pain (nine [8%]), and diarrhoea (eight [7%]) in the elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide group; and bronchitis (six [11%]), vitamin D deficiency (four [7%]), and arthralgia (four [7%]) in the tenofovir disoproxil fumarate group. 22 (20%) participants in the elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide group and one (2%) participant in the tenofovir disoproxil fumarate group had an adverse event that was considered to be related to treatment. No treatment-related serious adverse events were observed. The proportions of adverse events leading to premature treatment discontinuation were similar between groups (four [4%] in the elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide group; and one (2%) in the tenofovir disoproxil fumarate group). INTERPRETATION The significantly improved bone mineral density, overall safety, and efficacy data show the feasibility of switching from a regimen containing tenofovir disoproxil fumarate to elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in virologically suppressed people living with HIV aged 60 years or older. FUNDING Gilead Sciences.
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Effects of denosumab on bone mineral density in Japanese women with osteoporosis treated with aromatase inhibitors for breast cancer.
Nakatsukasa, K, Koyama, H, Ouchi, Y, Sakaguchi, K, Fujita, Y, Matsuda, T, Kato, M, Konishi, E, Taguchi, T
Journal of bone and mineral metabolism. 2019;(2):301-306
Abstract
Adjuvant aromatase inhibitor (AI) therapy, for hormone receptor-positive breast cancer, in postmenopausal women is associated with bone loss, leading to an increased risk of fractures. Denosumab, an antibody raised against the receptor activator of nuclear factor-κB ligand, has been proven to protect against AI-induced bone loss. Hence, we aimed to determine whether denosumab is effective in postmenopausal Japanese women with osteoporosis, treated with AI. We prospectively evaluated the bone mineral density (BMD) in the lumbar spine and the bilateral femoral neck in 102 postmenopausal women with clinical hormone receptor-positive breast cancer, stages I-IIIA, during a postoperative period of 12 months. The other inclusion criteria for this study were: women that should receive AIs as adjuvant therapy and those with evidence of osteoporosis (lumbar spine or bilateral femoral neck BMD, equivalent to T-score classification of ≤ - 2.5) upon enrollment. The patients received supplemental calcium, vitamin D, and 60 mg of subcutaneous denosumab every 6 months. The BMD of the lumber spine increased by 4.9 and 6.6% at 6 and 12 months, respectively. An increase in BMD was observed at the femoral neck, bilaterally. Hypocalcemia ≥ grade 2, osteonecrosis of the jaw, and non-traumatic clinical fracture were not observed in this study. Our findings revealed that biannual treatment with denosumab is associated with a great increase of BMD in Japanese women receiving adjuvant AI therapy, irrespective of their previous history of AI therapy.
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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.