scholarly journals Prevention of Bone Loss in Survivors of Breast Cancer: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

2007 ◽  
Vol 92 (1) ◽  
pp. 131-136 ◽  
Author(s):  
Susan L. Greenspan ◽  
Rajib K. Bhattacharya ◽  
Susan M. Sereika ◽  
Adam Brufsky ◽  
Victor G. Vogel
Keyword(s):  
Breast Cancer ◽  
Bone Loss ◽  
Breast Cancer Survivors ◽  
Collagen Type ◽  
Collagen Type I ◽  
Controlled Clinical Trial ◽  
Type I ◽  
Mineral Density ◽  
Double Blind ◽  
Type I Procollagen

Abstract Background: Few data are available on the safety and efficacy of once-weekly oral bisphosphonate therapy in breast cancer survivors. Objective: Our objective was to determine whether risedronate, 35 mg weekly, is efficacious and safe in preventing bone loss associated with chemotherapy-induced menopause. Design: The study was a randomized, double-blind, placebo-controlled clinical trial over 12 months. Setting and Participants: Participants included 87 newly postmenopausal women with status post chemotherapy, recruited from a breast cancer clinic in an academic medical center. Intervention: Participants were randomly assigned to receive risedronate 35 mg/wk or placebo. Main Outcome Measures: The primary outcomes were the 12-month changes in spine and hip bone mineral density. Secondary outcomes included changes in markers of bone resorption (urine N-telopeptide cross-linked collagen type I) and formation (osteocalcin, N-terminal propeptide of type I procollagen, and bone-specific alkaline phosphatase). Results: After 12 months, bone mineral density increased by 1.2% at the spine and 1.3% at the hip in women on risedronate vs. significant decreases for women in the placebo group of 0.9% at the spine and 0.8% at the hip (P < 0.01, difference between groups). N-telopeptide cross-linked collagen type I, a marker of bone resorption, decreased by 19.3%, and N-terminal propeptide of type I procollagen, a marker of bone formation, decreased by 26.6% in participants on active therapy compared with increases in the control group. Risedronate was well tolerated, and the retention rate was 95% at 1 yr. Conclusions: Risedronate once weekly prevented bone loss and reduced bone turnover in women with breast cancer treated with chemotherapy. Early measures to prevent bone loss should be considered in this cohort of breast cancer survivors.

scholarly journals Denosumab in transfusion-dependent thalassemia osteoporosis: a randomized, placebo-controlled, double-blind phase 2b clinical trial

2018 ◽  
Vol 2 (21) ◽  
pp. 2837-2847 ◽  
Author(s):  
Ersi Voskaridou ◽  
Ioannis Ntanasis-Stathopoulos ◽  
Athanasios Papaefstathiou ◽  
Dimitrios Christoulas ◽  
Maria Dimopoulou ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Mineral ◽  
Collagen Type ◽  
Collagen Type I ◽  
Tartrate Resistant Acid Phosphatase ◽  
Type I ◽  
Mineral Density ◽  
Double Blind ◽  
Bone Specific Alkaline Phosphatase ◽  
Dickkopf 1

Abstract Denosumab (DNM) is a fully human monoclonal antibody against the receptor activator of nuclear factor kappa-B ligand (RANKL) that has been licensed for the treatment of different types of osteoporosis. However, the prospective data for the evaluation of DNM efficacy on transfusion-dependent thalassemia (TDT)–induced osteoporosis are rather limited. Thus, we conducted a randomized, placebo-controlled, double-blind, phase 2b clinical trial to evaluate DNM in TDT osteoporosis. Patients were assigned to receive either 60 mg DNM (n = 32) or placebo (n = 31) subcutaneously on day 0 and 180 during a total of 12 months of follow-up. The percentage increase of L1-L4 bone mineral density was higher in the DNM group than the placebo group (5.92% ± 5.25% vs 2.92% ± 5.56%, respectively; P = .043), whereas the advantage of DNM regarding wrist bone mineral density was much higher compared with placebo (−0.26% ± 5.31% vs −3.92% ± 8.71%, respectively; P = .035). No grade 3 or 4 toxicity was observed. DNM reduced pain scores that remained unaltered in the placebo group. DNM showed a significant reduction of soluble RANKL (sRANKL), sRANKL/osteoprotegerin ratio, C-telopeptide of collagen type I, tartrate-resistant acid phosphatase isoform-5b, and bone-specific alkaline phosphatase between baseline and the 12th month (P < .01 for all comparisons) without changes in dickkopf-1, sclerostin, and osteocalcin. On the contrary, placebo patients showed an increase in sRANKL, osteoprotegerin, dickkopf-1, sclerostin, C-telopeptide of collagen type I, tartrate-resistant acid phosphatase isoform-5b, and bone-specific alkaline phosphatase during the study period (P < .01 for all comparisons). In conclusion, DNM increased lumbar spine and wrist bone mineral density and reduced pain and bone remodeling markers, and thus it is another valuable option for the management of TDT-induced osteoporosis. This trial was registered at www.clinicaltrials.gov as #NCT02559648.

Bisphosphonate risedronate prevents bone loss in women with artificial menopause due to chemotherapy of breast cancer: a double-blind, placebo-controlled study.

1997 ◽  
Vol 15 (3) ◽  
pp. 955-962 ◽  
Author(s):  
P D Delmas ◽  
R Balena ◽  
E Confravreux ◽  
C Hardouin ◽  
P Hardy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lumbar Spine ◽  
Bone Loss ◽  
Femoral Neck ◽  
White Women ◽  
Treatment Withdrawal ◽  
Controlled Study ◽  
Treatment Needs ◽  
Mineral Density ◽  
Double Blind

PURPOSE To determine the effectiveness and safety of the bisphosphonate risedronate in preventing bone loss in young women with breast cancer and early menopause induced by chemotherapy who are at major risk for the development of postmenopausal osteoporosis. PATIENTS AND METHODS Fifty-three white women, aged 36 to 55 years, with breast cancer and artificially induced menopause were stratified according to prior tamoxifen use. Thirty-six patients received tamoxifen (20 mg/d). Within each stratum, patients were randomly assigned to receive risedronate (n = 27) or placebo (n = 26). Treatment consisted of eight cycles oral risedronate 30 mg/d or placebo daily for 2 weeks followed by 10 weeks of no drug (12 weeks per cycle). Patients were monitored for a third year without treatment. RESULTS Main outcomes of the study were changes in lumbar spine and proximal femur (femoral neck, trochanter, and Ward's triangle) bone mineral density (BMD), and biochemical markers of bone turnover. In contrast to a significant decrease of BMD at the lumbar spine and hip in the placebo group, there was an increase in BMD in the risedronate group. On treatment withdrawal, bone loss ensued, which suggests that treatment needs to be continuous to maintain a protective effect on bone mass. At 2 years, the mean difference (+/- SEM) between groups was 2.5% +/- 1.2%, (95% confidence interval [CI], 0.2 to 4.9) at the lumbar spine (P = .041) and 2.6% +/- 1.1%, (95% CI, 0.3 to 4.8) at the femoral neck (P = .029). Similar results were observed at the hip trochanter. Results by stratum indicate a beneficial, although partial, effect of tamoxifen in reducing bone loss. Risedronate was well tolerated and showed a good safety profile, with no evidence of laboratory abnormalities. CONCLUSION Risedronate appears to be a safe treatment that prevents both trabecular and cortical bone loss in women with menopause induced by chemotherapy for breast cancer.

Association of Collagen Type I α1 Gene Polymorphism with Bone Mineral Density in Osteoporotic Women in Serbia

2010 ◽  
Vol 19 (7) ◽  
pp. 1299-1303 ◽  
Author(s):  
Katarina Trajkovic ◽  
Milka Perovic ◽  
Aleksej Tarasjev ◽  
Nada Pilipovic ◽  
Vera Popovic ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Gene Polymorphism ◽  
Bone Mineral ◽  
Collagen Type ◽  
Collagen Type I ◽  
Type I ◽  
Mineral Density

Modeling Sympathetic Hyperactivity in Alzheimer’s Related Bone Loss

2021 ◽  
pp. 1-12
Author(s):  
Robert A. Culibrk ◽  
Ahmad S. Arabiyat ◽  
Carisa A. DeKalb ◽  
Mariah S. Hahn
Keyword(s):  
Bone Loss ◽  
Sympathetic Neurons ◽  
Cell Types ◽  
Collagen Type I ◽  
Type I ◽  
Mineral Density ◽  
Necrosis Factor Alpha ◽  
Glycol Diacrylate ◽  
Tnf Α

Background: A significant subset of patients with Alzheimer’s disease (AD) exhibit low bone mineral density and are therefore more fracture-prone, relative to their similarly aged neurotypical counterparts. In addition to chronic immune hyperactivity, behavioral dysregulation of effector peripheral sympathetic neurons—which densely innervate bone and potently modulate bone remodeling—is implicated in this pathological bone reformation. Objective: Thus, there exists a pressing need for a robust in vitro model which allows interrogation of the paracrine interactions between the putative mediators of AD-related osteopenia: sympathetic neurons (SNs) and mesenchymal stem cells (MSCs). Methods: Toward this end, activated SN-like PC12 cells and bone marrow derived MSCs were cultured in poly(ethylene glycol) diacrylate (PEGDA) hydrogels in the presence or absence of the AD-relevant inflammatory cytokine tumor necrosis factor alpha (TNF-α) under mono- and co-culture conditions. Results: PC12s and MSCs exposed separately to TNF-α displayed increased expression of pro-inflammatory mediators and decreased osteopontin (OPN), respectively. These data indicate that TNF-α was capable of inducing a dysregulated state in both cell types consistent with AD. Co-culture of TNF-α-activated PC12s and MSCs further exacerbated pathological behaviors in both cell types. Specifically, PC12s displayed increased secretion of interleukin 6 relative to TNF-α stimulated monoculture controls. Similarly, MSCs demonstrated a further reduction in osteogenic capacity relative to TNF-α stimulated monoculture controls, as illustrated by a significant decrease in OPN and collagen type I alpha I chain. Conclusion: Taken together, these data may indicate that dysregulated sympathetic activity may contribute to AD-related bone loss.

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