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Serum 25-hydroxy-vitamin D and the risk of fractures in the teriparatide versus risedronate VERO clinical trial.
Minisola, S, Marin, F, Kendler, DL, Geusens, P, Zerbini, CAF, Russo, LA, Casado, E, Fahrleitner-Pammer, A, Stepan, JJ, Lespessailles, E, et al
Archives of osteoporosis. 2019;(1):10
Abstract
PURPOSE Using data from the 2-year, randomized, double-dummy VERO trial, we examined the changes in 25-hydroxy-vitamin D (25[OH]D) concentrations over time, and whether the fracture risk reduction of teriparatide versus risedronate varies by baseline 25(OH)D sufficiency category. METHODS Postmenopausal women with established osteoporosis received subcutaneous daily teriparatide 20 μg or oral weekly risedronate 35 mg, with concomitant 500-1000 mg of elemental calcium and 400-800 IU/day of vitamin D supplements. Fracture endpoints were analyzed by predefined subgroups of 25(OH)D insufficient and sufficient patients. Heterogeneity of the treatment effect on fractures was investigated by logistic and Cox proportional hazards regression models. RESULTS At baseline, mean serum 25(OH)D was 31.9 ng/mL in the teriparatide group and 31.5 ng/mL in the risedronate group, and 16.8% and 17.9% of patients, respectively, were 25(OH)D insufficient. At month 6, the mean serum 25(OH)D concentration decreased in teriparatide-treated patients to 24.5 ng/mL (by approximately 23%) but remained relatively constant in risedronate-treated patients (32.2 ng/mL) (p < 0.001). Proportions of 25(OH)D insufficient patients at month 6 were 26.7% and 5.6%, respectively (p < 0.001). The risk reduction with teriparatide versus risedronate for any of the fracture endpoints did not significantly differ between subgroups by 25(OH)D sufficiency status at baseline, with nonsignificant (p > 0.1) treatment-by-25(OH)D interactions in all fracture analyses. CONCLUSIONS Serum 25(OH)D concentration decreases during teriparatide treatment. Fracture risk reduction with teriparatide versus risedronate did not significantly differ between the two groups of patients defined by baseline 25(OH)D. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01709110 EudraCT Number: 2012-000123-41.
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Effects of teriparatide in Chinese and Caucasian women with osteoporosis: bridging study on efficacy.
Xie, Z, Chen, Y, Gurbuz, S, Zhang, B, Li, Y, Bai, F, Chen, Y
Clinical interventions in aging. 2019;:959-968
Abstract
OBJECTIVE To bridge the efficacy and compare the safety of the 24-week teriparatide treatment in a Chinese osteoporosis study (NCT00414973) to a large international trial (FPT, NCT00670501) to determine whether long-term results from the international study were applicable to Chinese patients. METHODS In this post-hoc analysis, a propensity score matching method was used to select patients with similar baseline characteristics. Patients were female with osteoporosis at high risk of fracture, aged ≥55 years, and had no history of rheumatoid arthritis or corticosteroid use. Outcomes included percentage changes in lumbar-spine bone mineral density (LS-BMD) from baseline to 24 weeks, safety in matched-pair patients, and long-term percentage changes in LS-BMD and fragility fracture incidence in the matched fracture prevention trial (FPT) population. The determination of the acceptability of bridging results was based on the International Conference on Harmonization E5 guidelines. RESULTS A total number of 228 patients from each study were matched and paired. Patients were similar at baseline (P-values >0.33) except for ethnicity (98% Caucasian for FPT). For changes in LS-BMD from baseline to week 24, treatment with teriparatide showed significantly greater increases (P-values <0.001; least-squares mean difference: 5.0% in the Chinese study and 5.4% in FPT) than comparator (calcitonin/placebo). The safety profiles over 24 weeks were similar between two studies. For matched-pair FPT patients, long-term changes in LS-BMD were significantly greater (least-squares mean difference: 11.5%, P<0.001) and the fragility fracture rate was marginally lower in the teriparatide group compared with the placebo group (13.1% vs 22.3%, P=0.070). CONCLUSION Assuming similar pharmacokinetic profiles for teriparatide between populations, comparable increases in LS-BMD and consistent safety profiles within 24 weeks of the treatment suggest long-term LS-BMD results from the FPT may be applicable to Chinese population.
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Adherence to osteoporosis therapy after an upper extremity fracture: a pre-specified substudy of the C-STOP randomized controlled trial.
McAlister, FA, Ye, C, Beaupre, LA, Rowe, BH, Johnson, JA, Bellerose, D, Hassan, I, Majumdar, SR
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2019;(1):127-134
Abstract
UNLABELLED Despite their proven efficacy for secondary fracture prevention, long-term adherence with oral bisphosphonates is poor. INTRODUCTION To compare the effectiveness of two interventions on long-term oral bisphosphonate adherence after an upper extremity fragility fracture. METHODS Community-dwelling participants 50 years or older with upper extremity fragility fractures not previously treated with bisphosphonates were randomized to either a multi-faceted patient and physician educational intervention (the active control arm) vs. a nurse-led case manager (the study arm). Primary outcome was adherence (taking > 80% of prescribed doses) with prescribed oral bisphosphonates at 12 months postfracture between groups; secondary outcomes included rates of primary non-adherence and 24-month adherence. We also compared quality of life between adherent and non-adherent patients. RESULTS By 12 months, adherence with the initially prescribed bisphosphonate was similar (p = 0.96) in both groups: 38/48 (79.2%) in the educational intervention group vs. 66/83 (79.5%) in the case manager arm. By 24 months, adherence rates were 67% (32/48) in the educational intervention group vs. 53% (43/81) in case managed patients (p = 0.13). Primary non-adherence was 6% (11 patients) in the educational intervention group and 12% (21 patients) in the case managed group (p = 0.07). Prior family history of osteoporosis (aOR 2.1, 95% CI 1.0 to 4.4) and being satisfied with current medical care (aOR 2.3, 95% CI 1.1 to 4.8) were associated with better adherence while lower income (aOR 0.2, 95% CI 0.1 to 0.6, for patients with income < $30,000 per annum) was associated with poorer rates of adherence. There were no differences in health-related quality of life scores at baseline or during follow-up between patients who were adherent and those who were not. CONCLUSION While both interventions achieved higher oral bisphosphonate adherence compared to previously reported adherence rates in the general population, primary non-adherence and long-term adherence to bisphosphonates were similar in both arms. Adherence was influenced by family history of osteoporosis, satisfaction with current medical care, and income. TRIAL REGISTRATION ClinicalTrials.gov : NCT01401556.
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Denosumab Versus Risedronate in Glucocorticoid-Induced Osteoporosis: Final Results of a Twenty-Four-Month Randomized, Double-Blind, Double-Dummy Trial.
Saag, KG, Pannacciulli, N, Geusens, P, Adachi, JD, Messina, OD, Morales-Torres, J, Emkey, R, Butler, PW, Yin, X, Lems, WF
Arthritis & rheumatology (Hoboken, N.J.). 2019;(7):1174-1184
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OBJECTIVE Clinical trial results have shown that, in glucocorticoid-treated patients, treatment with denosumab 60 mg subcutaneously once every 6 months (Q6M) increased spine and hip bone mineral density (BMD) at month 12 significantly more than treatment with risedronate 5 mg orally once daily (QD). The present analysis was performed to compare efficacy and characterize safety through month 24. METHODS This phase III study enrolled men and women ≥18 years old who had received ≥7.5 mg daily prednisone or equivalent for <3 months (glucocorticoid-initiating) or for ≥3 months (glucocorticoid-continuing) before screening. All patients <50 years old had a history of osteoporotic fracture. Glucocorticoid-continuing patients ≥50 years old had T scores of -2.0 or less (or -1.0 or less with fracture history). Patients were randomized (1:1) to receive denosumab 60 mg subcutaneously Q6M or risedronate 5 mg orally QD for 24 months, with daily calcium and vitamin D. RESULTS Of 795 patients, 590 (74.2%) completed the study (in the glucocorticoid-initiating group, 109 of 145 patients treated with denosumab and 117 of 145 patients treated with risedronate; in the glucocorticoid-continuing group, 186 of 253 patients treated with denosumab and 178 of 252 patients treated with risedronate). Denosumab was superior to risedronate in increasing lumbar spine and total hip BMD at all time points assessed, among glucocorticoid-initiating patients (24-month lumbar spine: BMD increase of 6.2% versus 1.7%, respectively [P < 0.001]; 24-month total hip: BMD increase of 3.1% versus 0.0% [P < 0.001]) and among glucocorticoid-continuing patients (24-month lumbar spine: BMD increase of 6.4% versus 3.2% [P < 0.001]; 24-month total hip: BMD increase of 2.9% versus 0.5% [P < 0.001]). Adverse events, serious adverse events (including infections), and fractures were similar between treatment groups. CONCLUSION Denosumab was superior to risedronate in terms of increases in spine and hip BMD through month 24, and the safety profile was similar between treatment groups. Denosumab may offer a new osteoporosis treatment option for glucocorticoid-treated patients.
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Anti-fracture efficacy of zoledronate in subgroups of osteopenic postmenopausal women: secondary analysis of a randomized controlled trial.
Reid, IR, Horne, AM, Mihov, B, Stewart, A, Garratt, E, Wiessing, KR, Bolland, MJ, Bastin, S, Gamble, GD
Journal of internal medicine. 2019;(2):221-229
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BACKGROUND We recently reported that the administration of zoledronate every 18 months to osteopenic older women reduces the incidence of fractures. OBJECTIVE Here, we present a more detailed analysis of that trial to determine whether baseline clinical characteristics impact on the anti-fracture efficacy of this intervention. METHODS This is a prospective, randomized, placebo-controlled, double-blind trial in osteopenic postmenopausal women aged ≥ 65 years, to determine the anti-fracture efficacy of zoledronate. 2000 women were recruited using electoral rolls and randomized to receive 4 infusions of either zoledronate 5 mg or normal saline, at 18-month intervals. Each participant was followed for 6 years. Calcium supplements were not supplied. RESULTS Fragility fractures (either vertebral or nonvertebral) occurred in 190 women in the placebo group (227 fractures) and in 122 women in the zoledronate group (131 fractures), odds ratio (OR) 0.59 (95%CI 0.46, 0.76; P < 0.0001). There were no significant interactions between baseline variables (age, anthropometry, BMI, dietary calcium intake, baseline fracture status, recent falls history, bone mineral density, calculated fracture risk) and the treatment effect. In particular, the reduction in fractures appeared to be independent of baseline fracture risk, and numbers needed to treat (NNT) to prevent one woman fracturing were not significantly different across baseline fracture risk tertiles. CONCLUSIONS The present analyses indicate that the decrease in fracture numbers is broadly consistent across this cohort. The lack of relationship between NNTs and baseline fracture risk calls into question the need for BMD measurement and precise fracture risk assessment before initiating treatment in older postmenopausal women.
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Zoledronic acid combined with percutaneous kyphoplasty in the treatment of osteoporotic compression fracture in a single T12 or L1 vertebral body in postmenopausal women.
Zhang, J, Zhang, T, Xu, X, Cai, Q, Zhao, D
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2019;(7):1475-1480
Abstract
UNLABELLED We performed a 1-year prospective study to see whether zoledronic acid infusion combined with percutaneous kyphoplasty could provide more benefits in the treatment of T12 or L1 osteoporotic vertebral compression fracture (OVCF). INTRODUCTION To investigate and analyze the clinical effects of zoledronic acid (ZOL) in combination with percutaneous kyphoplasty (PKP) in the treatment of OVCF in postmenopausal women. METHODS Included in this study were 101 postmenopausal women patients with T12 or L1 OVCF who received PKP in our hospital between August 2015 and July 2017. They were randomly assigned to a zoledronic acid (ZOL) group (n = 50) or a control group (n = 51). Patients in ZOL group were treated preoperatively with IV infusion of 5 mg ZOL in combination with 0.25μg/d calcitriol and D3 600 mg/d calcium carbonate for a year. Patients in the control group were treated with the same dose of calcitriol and calcium carbonate D3 without ZOL. RESULTS There was no statistically significant difference in age, height, weight, body mass index (BMI), menopause age, and the fractured vertebral body between the two groups. At 6 and 12 months after treatment, bone mineral density (BMD) in ZOL group was higher than that in the control group (p < 0.01); bone markers (NMID, P1NP, and β-CTX) and the VAS score in ZOL group were significantly lower than those in the control group. No new fracture occurred in ZOL group. The incidence of recompression vertebral fracture (RVF) in the control group was 11.7%, while no RVF was detected in any patient in ZOL group. Mild adverse reactions in ZOL group were significantly higher than those in the control group, but all of them were relieved after symptomatic treatment. CONCLUSIONS ZOL IV infusion in combination with PKP is beneficial for the treatment of T12 or L1 OVCF.
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The LIFTMOR-M (Lifting Intervention For Training Muscle and Osteoporosis Rehabilitation for Men) trial: protocol for a semirandomised controlled trial of supervised targeted exercise to reduce risk of osteoporotic fracture in older men with low bone mass.
Harding, AT, Weeks, BK, Watson, SL, Beck, BR
BMJ open. 2017;(6):e014951
Abstract
INTRODUCTION The primary aim of the proposed study is to examine the efficacy of an 8-month supervised, high-intensity progressive resistance training and impact loading programme in comparison with a supervised machine-based isometric exercise training programme using the bioDensity system in older men with low bone mass. We will also determine the safety and acceptability of each exercise training mode. Intervention group responses will be compared with those of a self-selected, non-randomised control sample of sex-matched and age-matched men who will follow their usual lifestyle activities for 8 months. METHODS AND ANALYSIS Apparently healthy men over 50 years with low bone mass, screened for medical conditions and medications known to adversely affect bone health, will be recruited. Eligible participants will be randomly allocated to 8 months of either exercise programme with block randomisation based on presence or absence of osteoporosis medications. A twice-weekly, 30-minute, supervised exercise programme will be conducted for both groups. The primary outcome will be change in femoral neck areal bone mineral density determined by dual-energy X-ray absorptiometry (DXA). Secondary outcomes, assessed at baseline and 8 months, will include: DXA-derived whole-body, bilateral proximal femur and lumbar spine areal bone mineral density; proximal femur bone geometry and volumetric density extracted using three-dimensional hip analysis software; anthropometry; body composition; kyphosis; vertebral fracture assessment; physical function; safety (adverse events and injuries); and compliance. Intention-to-treat and per-protocol analyses will be conducted. DISCUSSION Whether a high-intensity, low-repetition progressive resistance training and impact loading programme or a machine-based isometric exercise programme can improve determinants of fracture risk, without causing injury, has not been examined in men. Determination of the efficacy, safety and acceptability of such programmes will facilitate formulation of future exercise guidelines for older men with low bone mass at risk of fragility fracture, a group who have previously been under-represented. ETHICS AND DISSEMINATION Participant confidentiality will be maintained with publication of results. The study has been granted ethical approval from the Griffith University Human Research Ethics Committee (Protocol number AHS/07/14/HREC). TRIAL REGISTRATION NUMBER Australian New Zealand Clinical Trials Registry (www.anzctr.org.au)ANZCTR12616000344493; Pre-results.
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Effects of Enhanced Exercise and Combined Vitamin D and Calcium Supplementation on Muscle Strength and Fracture Risk in Postmenopausal Chinese Women.
Xue, Y, Hu, Y, Wang, O, Wang, C, Han, G, Shen, Q, Deng, H, Jiang, Y, Li, M, Xia, W, et al
Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae. 2017;(3):345-351
Abstract
Objective To observe the effects of enhanced exercise and combined vitamin D and calcium supplementation on muscular strength and fracture occurrence in postmenopausal women with a high risk of osteoporosis.Methods Totally 614 postmenopausal women at high risk factors of osteoporosis were enrolled in Dongcheng district of Beijing and randomized into four groups:group A(control group,n=173),group B(regular Tai Chi exercise,n=171),group C(calcium 600 mg/d+VitD3 800 U/d,n=139),and group D[calcium 600 mg/d+25 hydroxyl vitamin D(25OHD) 0.25 μg/d,n=131].Muscular strength was measured at baseline and one and two years after intervention.Bone turnover markers were measured at baseline and during the two-year follow-up.Falls and fractures were recorded.Results The incidence of 25OHD<50 nmol/L was approximately 92.6%.During the follow-up,the left grip strength decreased significantly two years after intervention(t=-3.252,P=0.001)in group A.Right grip strength decreased significantly in group B(t=2.460,P=0.015)while left grip strength improved significantly in group C(t=-2.051,P=0.043)one year after intervention.In group D,muscular strength in both 12-month and 24-month did not change compared with baseline(both P>0.05).Furthermore,serum procollagen type I N-terminal propeptide elevated significantly in group A(t=-2.962,P=0.004),group B(t=-2.888,P=0.005),and group C(t=-2.441,P=0.016),whereas β-C-terminal telopeptide of type I collagen decreased significantly in group B(t=2.285,P=0.024)and group D(t=2.596,P=0.011)two years after intervention.Conclusion Enhanced exercise and combined calcium vitamin D supplementation may help sustain muscle strength in postmenopausal women,while calcium and vitamin D supplementation may improve muscular strength within a short period of time.
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Impact of 3-Monthly Vitamin D Supplementation Plus Exercise on Survival after Surgery for Osteoporotic Hip Fracture in Adult Patients over 50 Years: A Pragmatic Randomized, Partially Blinded, Controlled Trial.
Laiz, A, Malouf, J, Marin, A, Longobardi, V, de Caso, J, Farrerons, J, Casademont, J
The journal of nutrition, health & aging. 2017;(4):413-420
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OBJECTIVE To determine whether 3-monthly supplementation of an oral vitamin D widely used in Spain (calcifediol) plus daily exercise could influence survival at one and four years after surgery for osteoporotic hip fracture. DESIGN A pragmatic, randomized, partially single-blind placebo-controlled study. SETTING Patients admitted to a tertiary university hospital for acute hip fracture. PARTICIPANTS 675 healthy adult patients undergoing surgery for osteoporotic hip fracture were recruited from January 2004 to December 2007. INTERVENTION Patients were randomized to receive either 3-monthly oral doses of 3 mg calcifediol (Hidroferol Choque®) or placebo in the 12 months postsurgery. Patients who received calcifediol were also given an exercise programme. The placebo group received standard health recommendations only. MEASUREMENTS The primary endpoint was survival at 1 year and at 4 year follow-up. We also recorded new fractures, medical complications and anti-osteoporotic treatment compliance. RESULTS We included a total of 88 patients, aged 62 to 99 years. Mean age was 82 years and 88.6% were women. At 12 months, 10 (11.3%) patients had died, 9 of them, from the non-intervention group. At 4 years after surgery, 20 (22.7%) had died, 3 (3.4%) from the intervention group and 17 (19.3%) from the non-intervention group. At this time, survival curve analysis showed 93% survival in the intervention group and 62% in the non-intervention group (p=0.001). At 12-month follow up, there were 18 new fractures, 9 in each group. The non-intervention group had more medical complications, with significant differences at visit 2 (p = 0.04) and 3 (p = 0.02) but not at visit 4 (p = 0.18). No significant differences between groups were found regarding treatment compliance. CONCLUSION 3-monthly, oral supplements of 3 mg calcifediol plus daily exercise improved survival at one-year and four-year follow up after surgery for an osteoporotic hip fracture.
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[Effects of different treatments on patients with osteoporotic fracture after percutaneous kyphoplasty].
Wang, XF, Xu, B, Ye, XY, Yang, YY, Wang, GH
Zhongguo gu shang = China journal of orthopaedics and traumatology. 2015;(6):512-6
Abstract
OBJECTIVE To evaluate effects of different treatments on patients with osteoporotic vertebral fracture after percutaneous kyphoplasty in pain and function. METHODS From March 2010 to March 2012,138 patients (165 vertebrae) with thoracic and lumbar vertebral osteoporotic fracture were randomly divided into three groups (control group, treatment group and comprehensive group), 46 cases in each group, and all patients were treated by PKP. Control group were treated with calcium and calcitriol after operation, treatment group added salmon calcitonin see calcimar based on control group, comprehensive group added incrementality waist musculi dorsi function exercise based on treatment group. VAS, ODI scores and BMD before operation, 3 d, 2 weeks, 1 month, 6 months and 12 months after operation were detected and compared. RESULTS All operation were performed successfully,38 cases (45 vertebrae) in control group, 36 cases (44 vertebrae) in treatment group and 40 cases (49 vertebrae) were obtained complete following up, there was no significant meaning in following time among three groups (P>0.05). Postoperative VAS and ODI scores at 3 d, 2 weeks and 1 month among three groups were lower than that of before operation (P<0.01). Compared with control group, postoperative VAS score at 3 d, 2 weeks and 1 month were decreasedin treatment group and comprehensive group, but there was no significant meaning in ODI scores (P>0.05). At 6 and 12 months after operation,there was no significant differences in VAS and ODI between control group and treatment group (P>0.05), while VAS score in comprehensive group decreased much than other two groups,decreased continuously (P<0.01). At 12 months after operation, BMD among three groups were increased more than preoperative,and BMD in comprehensive group was more obviously than that of in control and treatment group. CONCLUSION PKP, an effective method for the treatment of thoracic and lumbar vertebral osteoporotic fracture, could improve short-term clinical effects by adding calcitonin with calcium supplements and activated vitamin D. Waist musculi dorsi function exercise could improve long-term clinical effects of PKP and improve quality of life.