scholarly journals Effect of Stopping Risedronate after Long-Term Treatment on Bone Turnover

2011 ◽  
Vol 96 (11) ◽  
pp. 3367-3373 ◽  
Author(s):  
Richard Eastell ◽  
Rosemary A. Hannon ◽  
Dietrich Wenderoth ◽  
Jesus Rodriguez-Moreno ◽  
Andrzej Sawicki
Keyword(s):  
Postmenopausal Women ◽  
Type I Collagen ◽  
Term Treatment ◽  
Type I ◽  
Mineral Density ◽  
Open Label ◽  
Treatment Groups ◽  
Total Hip ◽  
Long Term Treatment ◽  
Hip Bmd

Abstract Context: Determining how quickly bisphosphonate treatment effects begin to regress is crucial when considering termination of treatment. Objective: Our objective was to assess the effects of 1 yr discontinuation of risedronate use in postmenopausal women with osteoporosis who had previously received risedronate for 2 or 7 yr. Design and Setting: Before initiation of the current study, placebo/5-mg-risedronate patients had received placebo for 5 yr and risedronate for 2 yr, whereas 5-mg-risedronate patients had received risedronate for a total of 7 yr. Risedronate was then discontinued for 1 yr (yr 8). Patients: Postmenopausal women with osteoporosis who had previously completed the 3-yr Vertebral Efficacy with Risedronate Therapy MultiNational (VERT-MN) pivotal trial, plus a 2-yr extension comparing risedronate or placebo for a total of 5 yr, followed by 2 yr of open-label risedronate treatment were enrolled in these trial extensions. Main Outcome Measures: Evaluations included changes in type I collagen cross-linked N-telopeptide (NTX)/creatinine (Cr) and bone mineral density (BMD) values, fracture incidence, and adverse events. Results: After 1 yr of risedronate discontinuation, NTX/Cr levels increased toward baseline in both patient groups vs. the values at the end of yr 7. In both treatment groups, off-treatment total hip and femoral trochanter BMD values decreased, whereas lumbar spine and femoral neck BMD were maintained or slightly increased. The adverse event profiles were similar between the two treatment groups during yr 8. Conclusions: One year of discontinuation of risedronate treatment in patients who had received 2 or 7 yr of risedronate therapy led to increases in NTX/Cr levels toward baseline and decreases in femoral trochanter and total hip BMD.

scholarly journals Effects of denosumab in Japanese rheumatoid arthritis patients treated with conventional anti-rheumatic drugs: 36-month extension of a phase 3 study

2021 ◽  
pp. jrheum.201376
Author(s):  
Yoshiya Tanaka ◽  
Tsutomu Takeuchi ◽  
Satoshi Soen ◽  
Hisashi Yamanaka ◽  
Toshiyuki Yoneda ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Type I Collagen ◽  
Joint Destruction ◽  
Term Treatment ◽  
Drug Discontinuation ◽  
Type I ◽  
Mineral Density ◽  
Phase 3 ◽  
Long Term Treatment

Objective To evaluate safety and efficacy of long-term denosumab 60 mg every 6 (Q6M) or 3 months (Q3M) in rheumatoid arthritis (RA) patients. Methods This 12-month, randomised, double-blind, placebo-controlled, multicentre phase 3 trial with an open-label extension period from 12 to 36 months (DESIRABLE) enrolled Japanese RA patients treated with placebo for 12 months then denosumab Q6M (P/Q6M) or denosumab Q3M (P/Q3M); denosumab Q6M for 36 months (Q6M/Q6M); or denosumab Q3M for 36 months (Q3M/Q3M). Efficacy was assessed by van der Heijde modified total Sharp (mTSS), bone erosion (ES), and joint space narrowing (JSN) scores. Results Long-term treatment better maintained mTSS and ES suppression in the P/Q3M and Q3M/Q3M versus P/Q6M and Q6M/Q6M groups; changes from baseline in total mTSS at 36 months were 2.8 (standard error 0.4), 1.7 (0.3), 3.0 (0.4), and 2.4 (0.3), respectively; corresponding changes in ES were 1.3 (0.2), 0.4 (0.2), 1.4 (0.2), and 1.1 (0.2). No JSN effect was observed. Bone mineral density consistently increased in all groups after denosumab initiation, regardless of concomitant glucocorticoid administration. Serum C-telopeptide of type I collagen decreased rapidly at 1-month post-denosumab administration (both in the initial 12- month [Q3M, Q6M groups] and long-term treatment [P/Q3M, P/Q6M groups] phases). Adverse event incidence leading to study drug discontinuation was similar across treatment groups. Conclusion Denosumab treatment maintained inhibition of progression of joint destruction up to 36 months. Based on effects on ES progression, higher dosing frequency at an earlier treatment stage may be needed to optimise treatment. Denosumab was generally well tolerated.

ZOOM: A prospective, randomized trial of zoledronic acid (ZOL; q 4 wk vs q 12 wk) for long-term treatment in patients with bone-metastatic breast cancer (BC) after 1 yr of standard ZOL treatment.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9005-9005 ◽  
Author(s):  
Dino Amadori ◽  
Massimo Aglietta ◽  
Barbara Alessi ◽  
Lorenzo Gianni ◽  
Toni Ibrahim ◽  
...  
Keyword(s):  
Randomized Trial ◽  
Type I Collagen ◽  
Metastatic Breast ◽  
Term Treatment ◽  
Phase Iii ◽  
Morbidity Rate ◽  
Type I ◽  
Open Label ◽  
Long Term Treatment

9005 Background: ZOL (4 mg q 4 wk) is an established therapy for reducing the risk of debilitating skeletal-related events (SREs) in patients (pts) with bone metastases (mets) from BC. As BC treatments continue to improve pt survival, long-term SRE-reduction is increasingly important, and evaluation of modified ZOL dosing to retain efficacy with reduced adverse events (AEs) is warranted. Methods: ZOOM, a phase III prospective, randomized, open-label, multicenter study, assessed the safety and efficacy of quarterly (4 mg q 12 wk; Arm 1) vs monthly (4 mg q 4 wk; Arm 2) ZOL for ~1 yr in pts with BC who have ≥ 1 bone met, and have received ~1 yr of prior ZOL treatment (9 to 12 doses over ≤ 15 months; last dose ≤ 3 months prior). The primary endpoint was skeletal morbidity rate (SMR; number of SREs/pt/yr). Sample size to detect non-inferiority with 80% power (1-sided a = 0.025) was 420 pts. Secondary endpoints included time to first SRE, bone pain, bone marker (N-telopeptide of type I collagen; NTX) levels, and safety. Results: 425 pts were enrolled (209 in Arm 1; 216 in Arm 2); arms were well balanced for pt and disease characteristics, and anticancer therapies. SMR was similar between arms: 0.26 (95% confidence interval [CI] = 0.15, 0.37) in Arm 1 vs 0.22 (95% CI = 0.14, 0.29) in Arm 2; between-arms difference = 0.04 (upper limit of 1-tailed 97.5% CI = 0.17). Despite the proximity of 0.17 to the adjusted non-inferiority margin (0.19), the non-inferiority of Arm 1 vs 2 remains statistically significant. Safety analyses showed that ZOL was well tolerated. Renal AEs were reported in similar proportions of pts in both arms; 7 cases of osteonecrosis of the jaw were reported (1.65% overall; 4 cases in Arm 1 vs 3 in Arm 2). Conclusions: ZOOM is the first randomized trial to compare ZOL q 12 wk vs ZOL q 4 wk in BC pts after 1 yr of standard ZOL therapy. SMR was similar between arms. Limitations in study design suggest the need to confirm non-inferiority of ZOL q 12 wk in other ongoing phase III trials.

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.

Prevention of Aromatase Inhibitor–Induced Bone Loss Using Risedronate: The SABRE Trial

2010 ◽  
Vol 28 (6) ◽  
pp. 967-975 ◽  
Author(s):  
Catherine Van Poznak ◽  
Rosemary A. Hannon ◽  
John R. Mackey ◽  
Mario Campone ◽  
Justus P. Apffelstaedt ◽  
...  
Keyword(s):  
Lumbar Spine ◽  
Postmenopausal Women ◽  
Fragility Fracture ◽  
Group Treatment ◽  
Mineral Density ◽  
Double Blind ◽  
Total Hip ◽  
Hormone Receptor Positive ◽  
Hip Bmd ◽  
To Receive

PurposeTo investigate the management of bone health in women with early breast cancer (EBC) who were scheduled to receive anastrozole.Patients and MethodsPostmenopausal women with hormone receptor–positive EBC were assigned to one of three strata by risk of fragility fracture. Patients with the highest risk (H) received anastrozole 1 mg/d plus risedronate 35 mg/wk orally. Patients with moderate-risk (M) were randomly assigned in a double-blind manner to anastrozole and risedronate (A + R) or to anastrozole and placebo (A + P). Patients with lower-risk (L) received anastrozole (A) alone. Calcium and vitamin D were recommended for all patients. Lumbar spine and total hip bone mineral density (BMD) were assessed at baseline, 12 months, and 24 months.ResultsAt 24 months, in the M group, treatment with A + R resulted in a significant increase in lumbar spine and total hip BMD compared with A + P treatment (2.2% v −1.8%; treatment ratio, 1.04; P < .0001; and 1.8% v −1.1%; treatment ratio, 1.03; P < .0001, respectively). In the H stratum, lumbar spine and total hip BMD increased significantly (3.0%; P = .0006; and 2.0%; P = .0104, respectively). Patients in the L stratum showed a significant decrease in lumbar spine BMD (−2.1%; P = .0109) and a numerical decrease in total hip BMD (−0.4%; P = .5988). Safety profiles for anastrozole and risedronate were similar to those already established.ConclusionIn postmenopausal women at risk of fragility fracture who were receiving adjuvant anastrozole for EBC, the addition of risedronate at doses established for preventing and treating osteoporosis resulted in favorable effects in BMD during 24 months.

Urinary Phthalate Biomarkers and Bone Mineral Density in Postmenopausal Women

2021 ◽  
Author(s):  
Katherine W Reeves ◽  
Gabriela Vieyra ◽  
Nydjie P Grimes ◽  
Jaymie Meliker ◽  
Rebecca D Jackson ◽  
...  
Keyword(s):  
Femoral Neck ◽  
Postmenopausal Women ◽  
Endocrine Disrupting Chemicals ◽  
Estimating Equation ◽  
Mineral Density ◽  
Cross Sectional ◽  
Total Hip ◽  
Physiologic Function ◽  
Hip Bmd ◽  
Nested Case Control

Abstract Background Phthalates are endocrine-disrupting chemicals that could disrupt normal physiologic function, triggering detrimental impacts on bone. We evaluated associations between urinary phthalate biomarkers and BMD in postmenopausal women participating in the prospective Women’s Health Initiative (WHI). Methods We included WHI participants enrolled in the BMD substudy and selected for a nested case-control study of phthalates and breast cancer (N=1255). We measured thirteen phthalate biomarkers and creatinine in 2-3 urine samples per participant collected over 3 years, when all participants were cancer-free. Total hip and femoral neck BMD were measured at baseline and year 3, concurrent with urine collection, via dual energy x-ray absorptiometry. We fit multivariable generalized estimating equation models and linear mixed effects models to estimate cross-sectional and longitudinal associations, respectively, with stratification on postmenopausal hormone therapy (HT) use. Results In cross-sectional analyses, mono-3-carboxypropyl phthalate and the sum of di-isobutyl phthalate metabolites were inversely associated with total hip BMD among HT non-users, but not among HT users. Longitudinal analyses showed greater declines in total hip BMD among HT non-users and with highest concentrations of mono-3-carboxyoctyl phthalate (-1.80%, 95% CI -2.81 – -0.78%) or mono-carboxynonyl phthalate (-1.84%, 95% CI -2.80 – -0.89%); similar associations were observed with femoral neck BMD. Among HT users, phthalate biomarkers were not associated with total hip or femoral neck BMD change. Discussion Certain phthalate biomarkers are associated with greater percent decreases in total hip and femoral neck BMD. These findings suggest that phthalate exposure may have clinically important effects on BMD, and potentially fracture risk.

Low Aromatase Activity and Estradiol/Sex Hormone Binding Globulin Ratio are Associated with Total Hip Bone Mineral Density and the Presence of Osteoporosis: A Study in Chinese Postmenopausal Women

2018 ◽  
Vol 50 (01) ◽  
pp. 65-72 ◽  
Author(s):  
Hai-Juan Liu ◽  
Jun Yan ◽  
Yan Li ◽  
Fang-Yuan Zhou ◽  
Xu-Dong Su ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Postmenopausal Women ◽  
Bone Mineral ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Aromatase Activity ◽  
Type I ◽  
Hormone Binding ◽  
Mineral Density ◽  
Total Hip

AbstractSeveral groups have reported the important role of estradiol (E2) and testosterone (T) in postmenopausal osteoporosis (PMOP). Because aromatase catalyzes the conversion of T to E2, the purpose of this study was to determine the influence of aromatase activity on the bone mineral density (BMD) in postmenopausal women. A total of 344 postmenopausal women were selected for this study. Serum E2, T, sex hormone-binding globulin (SHBG), calcium (Ca), alkaline phosphatase (ALP), C-terminal telopeptide of type I collagen (CTX), and procollagen type I amino-terminal propeptide (PINP) were examined. The E2/T was positively associated with total hip BMD and PINP (p<0.05). When E2/T was divided into quartiles, participants in lower quartiles of E2/T were likely to have higher PINP and lower BMD (p<0.05). The prevalence of osteoporosis significantly increased as E2/T ratio decreased. The receiver operating characteristic (ROC) curves were constructed for serum E2, free E2 index (FEI), and E2/T, to assess their diagnostic accuracy in PMOP. The overall area under the curve (AUC) were 0.83 (95% CI=0.77–0.88) for E2, 0.87 (95% CI=0.82–0.92) for FEI, and 0.89 (95% CI=0.85–0.94), respectively. In conclusion, the study suggests that in postmenopausal women, aromatase activity could be an important determinant of skeletal health. The women with lower aromatase activity may have greater likelihood of PMOP and the E2/T was expected to be a valuable indicator for the prediction of PMOP and to monitor the process of osteoporosis.

scholarly journals Association between Geriatric Nutrition Risk Index and Skeletal Muscle Mass Index with Bone Mineral Density in Post-Menopausal Women Who Have Undergone Total Thyroidectomy

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1683
Author(s):  
Tai-Hua Chiu ◽  
Szu-Chia Chen ◽  
Hui-Chen Yu ◽  
Jui-Sheng Hsu ◽  
Ming-Chen Shih ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Total Thyroidectomy ◽  
Postmenopausal Women ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Mineral Density ◽  
Total Hip ◽  
T Score ◽  
Hip Bmd ◽  
Skeletal Muscle Mass Index

Background: Osteoporosis is highly prevalent in postmenopausal women and may result in fractures and disabilities. Total thyroidectomy has also been associated with loss of bone mass. The aim of this cross-sectional study was to evaluate associations among nutritional status, skeletal muscle index and markers of bone turnover to bone mineral density in postmenopausal women who had undergone total thyroidectomy. Methods: Fifty postmenopausal women who had undergone total thyroidectomy were included. Body composition was measured using dual-energy X-ray absorptiometry (DXA). The Geriatric Nutritional Risk Index (GNRI) was calculated using baseline body weight and serum albumin level. Skeletal muscle mass index was calculated as the appendicular skeletal muscle mass (ASM) divided by the height squared and assessed using DXA. Results. Multivariate stepwise linear regression analysis showed that a low GNRI was significantly associated with low lumbar spine bone mineral density (BMD) and T-score, and that a low ASM/height2 was significantly associated with low femoral neck BMD and T-score. A low vitamin D level was significantly associated with low femoral neck BMD and T-score and low total hip BMD and T-score. A high bone alkaline phosphatase (ALP) level was significantly associated with low femoral neck T-score and low total hip BMD and T-score. A low insulin-like growth factor-1 (IGF-1) was significantly associated with low total hip BMD and T-score. Conclusion: In the postmenopausal women who had undergone total thyroidectomy in this study, BMD was positively associated with GNRI, skeletal muscle mass index, and levels of vitamin D and serum IGF-1, and inversely associated with bone ALP level. Nutritional status, skeletal muscle mass index and bone turnover biomarkers can be used to early identify patients with a high risk of osteoporosis in this high-risk group.

Efficacy of single or combined midodrine and pyridostigmine in orthostatic hypotension

Neurology ◽  
2017 ◽  
Vol 89 (10) ◽  
pp. 1078-1086 ◽  
Author(s):  
Jung-Ick Byun ◽  
Jangsup Moon ◽  
Do-Yong Kim ◽  
Hyerim Shin ◽  
Jun-Sang Sunwoo ◽  
...  
Keyword(s):  
Orthostatic Hypotension ◽  
Combined Therapy ◽  
Term Treatment ◽  
Open Label ◽  
Treatment Groups ◽  
Long Term Treatment ◽  
Secondary Endpoints ◽  
Orthostatic Symptoms

Objective:To evaluate the long-term (for up to 3 months) efficacy and safety of single or combined therapy with midodrine and pyridostigmine for neurogenic orthostatic hypotension (OH).Methods:This was a randomized, open-label clinical trial. In total, 87 patients with symptomatic neurogenic OH were enrolled and randomized to receive 1 of 3 treatments: midodrine only, pyridostigmine only, or midodrine + pyridostigmine. The patients were followed up at 1 and 3 months after treatment. The primary outcome measures were improvement in orthostatic blood pressure (BP) drop at 3 months. Secondary endpoints were improvement of the orthostatic BP drop at 1 month and amelioration of the questionnaire score evaluating OH-associated symptoms.Results:Orthostatic systolic and diastolic BP drops improved significantly at 3 months after treatment in all treatment groups. Orthostatic symptoms were significantly ameliorated during the 3-month treatment, and the symptom severity was as follows: midodrine only < midodrine + pyridostigmine < pyridostigmine only group. Mild to moderate adverse events were reported by 11.5% of the patients.Conclusions:Single or combination treatment with midodrine and pyridostigmine was effective and safe in patients with OH for up to 3 months. Midodrine was better than pyridostigmine at improving OH-related symptoms.Clinicaltrials.gov identifier:NCT02308124.Classification of evidence:This study provides Class IV evidence that for patients with neurogenic OH, long-term treatment with midodrine alone, pyridostigmine alone, or both midodrine and pyridostigmine is safe and has similar effects in improving orthostatic BP drop up to 3 months.

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