Effect of Letrozole Versus Placebo on Bone Mineral Density in Women With Primary Breast Cancer Completing 5 or More Years of Adjuvant Tamoxifen: A Companion Study to NCIC CTG MA.17

2006 ◽  
Vol 24 (22) ◽  
pp. 3629-3635 ◽  
Author(s):  
Edith A. Perez ◽  
Robert G. Josse ◽  
Kathleen I. Pritchard ◽  
James N. Ingle ◽  
Silvana Martino ◽  
...  

Purpose Aromatase inhibition depletes estrogen levels and may be associated with accelerated bone resorption. The National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) study MA.17B evaluated bone turnover markers and bone mineral density (BMD) in postmenopausal women randomly assigned to MA.17, a placebo-controlled trial of letrozole after standard adjuvant tamoxifen. Patients and Methods Eligible women had a baseline BMD T score of at least 2.0 in either the hip or L2-4 spine; all received calcium 500 mg and vitamin D 400 U daily. Percentage change in BMD (L2-L4 spine and hip) at 12 and 24 months, rate of osteoporosis, and change in markers of bone formation (serum bone alkaline phosphatase) and resorption (serum C-telopeptide and urine N-telopeptide) at 6, 12, and 24 months were compared. Results Two hundred twenty-six patients (122 letrozole, 104 placebo) were enrolled. Baseline characteristics were similar in the two groups, including BMD, median age of 60.7 years (81% < 70 years), and median follow-up of 1.6 years. At 24 months, patients receiving letrozole had a significant decrease in total hip BMD (−3.6% v −0.71%; P = .044) and lumbar spine BMD (−5.35% v −0.70%; P = .008). Letrozole increased urine N-telopeptide at 6, 12, and 24 months (P = .054, < .001, and .016, respectively). No patient went below the threshold for osteoporosis in total hip BMD, whereas at the L2-L4 (posteroanterior view), more women became osteoporotic by BMD while receiving letrozole (4.1% v 0%; P = .064). Conclusion After 5 years of adjuvant tamoxifen, subsequent letrozole causes a modest increase in bone resorption and reduction in bone mineral density in the spine and hip compared to placebo. Further follow-up is necessary to evaluate the long-term clinical implications of this difference.

2020 ◽  
Vol 14 ◽  
pp. 175346662096514
Author(s):  
Francois Maltais ◽  
Isabelle Schenkenberger ◽  
Pascal L. M. L. Wielders ◽  
Juan Ortiz de Saracho ◽  
Kenneth Chinsky ◽  
...  

Background: The relationship between inhaled corticosteroids and bone mineral density (BMD) remains uncertain despite extensive research. Methods: This was an international, multicenter, randomized, double-blind, parallel-group, 3-year noninferiority study. Patients with chronic obstructive pulmonary disease (COPD) (⩾40 years of age; smoking history ⩾10 pack years) and at least one native hip evaluable for BMD were enrolled and randomized 1:1, stratified by sex, to treatment with vilanterol (VI) 25 µg or fluticasone furoate/vilanterol (FF/VI) 100 µg/25 µg. BMD measurements were taken via dual-energy X-ray absorptiometry every 6 months. The primary endpoint was assessment of the noninferiority of change from baseline in total hip BMD per year at the −1% noninferiority level. Change from baseline in BMD at the lumbar spine and BMD measurements by sex were secondary endpoints. Incidences of COPD exacerbations and bone fractures throughout the study were also recorded. Results: Of 283 randomized patients, 170 (60%) completed the study. Noninferiority was demonstrated for FF/VI versus VI with regards to change from baseline in total hip BMD per year, with changes of −0.27% and 0.18%, respectively, and a treatment difference of −0.46% per year [95% confidence interval (CI) −0.97 to 0.06]. The treatment difference for FF/VI versus VI regarding lumbar spine BMD was −0.51% per year (95% CI −1.11 to 0.10). COPD exacerbations and bone fracture rates were similar between treatment groups. Conclusion: FF/VI showed noninferiority to VI for change from baseline in total hip BMD per year, when assessed at the −1% noninferiority margin in a combined sample of men and women with COPD. The reviews of this paper are available via the supplemental material section.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marcel M. Nejatian ◽  
Salar Sobhi ◽  
Blake N. Sanchez ◽  
Kathryn Linn ◽  
Laurens Manning ◽  
...  

AbstractManagement of diabetes-related foot ulceration (DFU) includes pressure offloading resulting in a period of reduced activity. The metabolic effects of this are unknown. This study aims to investigate changes in bone mineral density (BMD) and body composition 12 weeks after hospitalisation for DFU. A longitudinal, prospective, observational study of 22 people hospitalised for DFU was conducted. Total body, lumbar spine, hip and forearm BMD, and total lean and fat mass were measured by dual-energy X-ray absorptiometry (DXA) during and 12 weeks after hospitalisation for DFU. Significant losses in total hip BMD of the ipsilateral limb (− 1.7%, p < 0.001), total hip BMD of the contralateral limb (− 1.4%, p = 0.005), femoral neck BMD of the ipsilateral limb (− 2.8%, p < 0.001) and femoral neck BMD of the contralateral limb (− 2.2%, p = 0.008) were observed after 12 weeks. Lumbar spine and forearm BMD were unchanged. HbA1c improved from 75 mmol/mol (9.2%) to 64 mmol/mol (8.0%) (p = 0.002). No significant changes to lean and fat mass were demonstrated. Total hip and femoral neck BMD decreased bilaterally 12 weeks after hospitalisation for DFU. Future research is required to confirm the persistence and clinical implications of these losses.


2018 ◽  
Vol 29 (2) ◽  
pp. 153-160 ◽  
Author(s):  
Davey MJM Gerhardt ◽  
José MH Smolders ◽  
Elisabeth A Roovers ◽  
Ton AJM Rijnders ◽  
Job LC van Susante

Introduction: We studied whether acetabular bone mineral density (BMD) is better preserved after resurfacing hip arthroplasty (RHA) versus small diameter metal-on-metal total hip arthroplasty (THA). Methods: This randomised controlled trial included 82 patients. BMD was measured in 5 periprosthetic regions of interest (ROI) with dual-energy absorptiometry (DEXA) preoperatively, at 3 and 6 months, 1, 2, 3 and 5 years postoperative. 34 RHA and 26 THA had a complete 5 years follow-up. 1 RHA and 1 THA were revised due to pseudotumour formation, 2 THA were revised because of recurrent dislocations and 1 RHA for avascular necrosis. Results: Overall an initial decrease in BMD was observed for both implants, stabilising after 2 years. 5 years after RHA a BMD change of +1% in upper cranial, –4% ( p < 0.01) in cranial, –8% ( p < 0.01) in craniomedial, –7% ( p < 0.01) in medial and +4% in caudal ROI compared to baseline values was seen. 5 years after THA a BMD change of –3% ( p = 0.01), –13% ( p < 0.01), –21% ( p < 0.01), –11% ( p < 0.01) and –2% for each respective ROI. The observed BMD decrease in different regions was structurally favouring the RHA-cup, with significantly higher levels in the cranial and craniomedial ROI. Conclusion: Acetabular BMD is better preserved behind a rigid press-fit convex cup in RHA compared to a titanium threaded cup in conventional THA in the cranial and craniomedial ROI. Despite of a theoretical higher stress-shielding behind the stiff acetabular component in RHA, compared to the more elastic threaded titanium THA-cup, bone depletion behind the RHA component does not seem to be of major concern. Registration: EudraCT (2006-005610-12)


2007 ◽  
Vol 156 (1) ◽  
pp. 123-127 ◽  
Author(s):  
Tomasz Miazgowski ◽  
Slawomir Pynka ◽  
Marzena Noworyta-Ziętara ◽  
Barbara Krzyzanowska-Świniarska ◽  
Robert Pikul

Objective: The risk of non-vertebral fractures is increased in men with type 1 diabetes (DM1) but studies have shown only moderately decreased or normal bone mineral density (BMD) in these patients. No previous studies have evaluated hip strength and geometry indices in DM1 patients. This study was therefore designed to characterize associations between BMD, dual X-ray absorptiometry (DXA)-based hip strength indices, metabolic control, and DM1chronic complications. Design and methods: The study was performed on 36 males aged 43.6 ± 5.1 years with long-lasting DM1 and 36 healthy males matched for age, weight, and height. BMD in lumbar spine, total hip, upper and lower part of the femoral neck, hip axis length, cross-sectional area and moment of inertia (CSMI), and glycated hemoglobin (HbA1c) were measured. Results: DM1 men had decreased spine BMD (P < 0.05) and normal total hip BMD in comparison with controls. Hip geometry and strength indices were comparable in both groups. However, M1 men had decreased CSMI and upper femur BMD but these differences did not reach statistical significance (P = 0.06). BMD changes and hip strength parameters did not correlate with HbA1c. Conclusions: Middle-aged DM1 men have decreased lumbar spine BMD, normal hip BMD and normal hip strength indices. These changes are not influenced by metabolic control and presence of chronic microvascular complications.


Author(s):  
Markus Herrmann ◽  
Marius Kraenzlin ◽  
Gerhard Pape ◽  
Marga Sand-Hill ◽  
Wolfgang Herrmann

AbstractBackground: Recently, increased plasma homocysteine (Hcy) has been suggested as an independent risk factor for osteoporotic fractures. Therefore, it is tempting to speculate that Hcy adversely affects bone metabolism. This study aimed to analyze the relation between Hcy and biochemical markers of bone metabolism and bone mineral density (BMD). Materials and methods: We investigated 143 peri- and post-menopausal women [median age (25th–75th percentile), 67 (57–75) years]. All subjects underwent a detailed medical examination, measurement of bone mineral density at lumbar spine (BMD-LS) and total hip (BMD-HIP), and fasting venous blood and urine sampling. Osteocalcin (OC), serum calcium (Ca), urinary desoxypyridinoline cross-links (DPD), osteoprotegerin (OPG) and soluble receptor activator of NF-κB ligand (sRANKL) were studied. Results: According to BMD subjects were classified as normal (n=24), osteopenic (n=51) or osteoporotic (n=68). Median Hcy did not differ between normal, osteopenic and osteoporotic subjects (p=0.647). Partial correlation analysis, controlling for the major confounders, age, creatinine, menopause and previous fractures, revealed significant correlations between Hcy and DPD (r=0.193, p=0.022), as well as between Hcy and Ca (r=0.170, p=0.045). After adjustment for the same confounders, subsequent regression analysis confirmed significant associations of Hcy with DPD and Ca. No significant relations could be observed between Hcy and BMD-LS, BMD-HIP, OC, OPG or sRANKL. Conclusion: Our results demonstrate weak, but significant, relations between Hcy and markers of organic and inorganic bone resorption, suggesting a mechanistic role of Hcy in bone metabolism. The relation between Hcy and bone resorption was not dependent on OPG or sRANKL.


2021 ◽  
Author(s):  
Yongze Zhang ◽  
Lingning Huang ◽  
Yuzhen Ke ◽  
Yuxi Lin ◽  
Ximei Shen ◽  
...  

Abstract Background The bone mineral density (BMD) did not increase significantly after the normalization of serum thyroid hormone levels. Studies on the effect of muscle mass on BMD in patients with Graves’ disease are scarce. This study aimed to determine the association of decreased muscle mass with reduced bone mineral density in patients with Graves’ disease. Methods A total of 758 patients with Graves’ at diagnosis (mean age 41.2 years) were enrolled for a cross-sectional study; of these, 287 patients were enrolled for a cohort study with a median follow-up of 24 months. Meanwhile, 1164 age- and sex-matched healthy controls participants were recruited. All participants underwent dual-energy x-ray absorptiometry and muscle mass index (ASMI) measurements. The changes in ASMI and BMD were calculated from the measurements made at a gap of 2 years. Results Compared with healthy controls participants, the BMD was still significantly lower after normalizing serum thyroid hormone levels (1.131 ± 0.268 vs. 1.07 ± 0.133, p < 0.05). ASMI was positively related to BMD in patients with Graves’ disease(lumbar BMD, r = 0.210; femoral neck BMD, r = 0.259;hip BMD, r = 0.235;P < 0.001) and this relationship still existed after successful anti-thyroid therapy(lumbar BMD, r = 0.169; femoral neck BMD, r = 0.281;hip BMD, r = 0.394;P < 0.001). Low muscle mass was associated with low BMD (OR, 1.426; 95% CI, 1.019–1.994). Moreover, improving the muscle mass led to changes in the bone mass of the femoral neck (OR, 0.420; 95% CI, 0.194–0.911) and hip (OR, 0.217; 95% CI, 0.092–0.511) during the follow-up period. However, this phenomenon was not observed in lumbar, and bone turnover markers. Conclusions The recovery of bone mass might be related to the recovery of muscle mass. Improving muscle mass might bring about changes in the bone mass of the femoral neck and hip. A site-related discrepancy was also observed. Patients with Graves’ disease should be helped in recovering muscle mass while administering anti-thyroid therapy.


2014 ◽  
Vol 99 (6) ◽  
pp. 2173-2180 ◽  
Author(s):  
Lian-Yu Lin ◽  
Li-Li Wen ◽  
Ta-Chen Su ◽  
Pau-Chung Chen ◽  
Chien-Yu Lin

Context: Perfluorooctanoic acid (PFOA) and perfluorooctane sulfate (PFOS) are used in a variety of products worldwide. However, the relationship among serum PFOA, PFOS concentration, bone mineral density (BMD), and the risk of fractures has never been addressed. Objectives: The study examined the association among serum PFOA, PFOS concentration, and lumbar spine and total hip BMD in the general US population. Design and Participants: We analyzed data on 2339 adults (aged ≧20 y) from the National Health and Nutrition Examination Survey conducted in 2005–2006 and 2007–2008 to determine the relationship among serum PFOA, PFOS concentration, and total lumbar spine and total hip BMD measured by dual-energy x-ray absorptiometry and history of fractures cross-sectionally. Results: After weighting for sampling strategy, a 1-U increase in the natural log-transformed serum PFOS level was associated with a decrease in total lumbar spine BMD by 0.022 g/cm2 (95% confidence interval −0.038, −0.007; P = .006) in women not in menopause. There was no association among PFOA, PFOS concentration, and self-reported fracture in adults. Conclusion: Serum PFOS concentration is associated with decreased total lumbar spine BMD in women not in menopause. However, the potential biological significance of this effect is marginal and subclinical in the general US population. Further studies are warranted to clarify the causal relationship between perfluorinated chemical exposure and BMD.


Author(s):  
Brandon S. Etheridge ◽  
David P. Beason ◽  
Robert R. Lopez ◽  
Jorge E. Alonso ◽  
Alan W. Eberhardt

Pelvic injuries due to lateral motor vehicle crashes continue to be a source of morbidity and mortality for accident victims as well as a serious problem for trauma surgeons and automotive safety engineers. In the present study, we sought to further explore the relationship between bone mineral density (BMD) measurements in the hip and pelvic fracture load and compression. We conducted experimental side impacts on intact lower torsos of female cadavers, building upon our previous work conducted on isolated bone-ligament structures. Significant linear relationships between pelvic fracture load/compression and total hip BMD emerged as further evidence that total hip bone mineral density may be a useful predictor of pelvic fracture risk. The presence of soft tissues increased resulting pelvic fracture loads as compared to those found in our previous isolated pelvic impacts.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 511-511 ◽  
Author(s):  
R. E. Coleman

511 Background: Since reporting the 1- and 2-year results from the ATAC trial bone sub-protocol, 68-month analysis results from the main ATAC trial have shown that, for postmenopausal women with invasive primary breast cancer, adjuvant treatment with anastrozole results in superior efficacy and tolerability compared with tamoxifen. Here we report 5-year bone mineral density (BMD) results from the monotherapy arms (anastrozole, n=81; tamoxifen, n=86) of the bone sub-protocol. Methods: Lumbar spine and total hip BMD were assessed by dual-energy X-ray absorptiometry at baseline and after 1, 2, and 5 years. Results: The median percentage changes in BMD at 1, 2, and 5 years, respectively, are shown in the table . Percentage changes in BMD from baseline to 5 years showed a statistically significant difference in favor of tamoxifen for both lumbar spine (treatment effect [percentage decrease of BMD on anastrozole relative to tamoxifen] −8.1; 95% confidence intervals [CI] −10.1, −6.1; p<0.0001) and total hip (treatment effect −7.4; 95% CI −9.6, −5.3; p<0.0001). For patients with data at baseline, 2, and 5 years, the rate of loss of lumbar spine BMD in the anastrozole group was significantly less from 2 to 5 years than from baseline to 2 years (mean difference in annual rate of change 0.0113, 95% CI 0.006, 0.017; p=0.0002), but there was no evidence of slowing down in the loss of total hip BMD. Five patients with osteopenia at baseline developed osteoporosis on treatment with anastrozole (4) or tamoxifen (1). No patients with normal BMD at baseline became osteoporotic at 5 years. Conclusions: Significant bone loss occurred throughout the 5 years in the anastrozole group, although there appeared to be a slowing down of the rate of bone loss in years 2–5. Although no patients with normal BMD at baseline had become osteoporotic at 5 years, regular monitoring of BMD and bone protection strategies are likely to be required in patients receiving anastrozole in the presence of pre-existing osteopenia. [Table: see text] [Table: see text]


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