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Osteoporosis: HELP
Articles by Kenneth G. Saag
Based on 100 articles published since 2010
(Why 100 articles?)
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Between 2010 and 2020, K. G. Saag wrote the following 100 articles about Osteoporosis.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4
1 Editorial How to use bisphosphonates safely and optimally. 2018

Jagpal, Aprajita / Saag, Kenneth G. ·Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA. ·Rheumatology (Oxford) · Pubmed #29165674.

ABSTRACT: -- No abstract --

2 Editorial Response to the American College of Physicians Osteoporosis Guideline, 2017 Update. 2017

Caplan, Liron / Hansen, Karen E / Saag, Kenneth G. ·University of Colorado Denver School of Medicine and Denver Veterans Affairs Medical Center, Denver, Colorado. · University of Wisconsin School of Medicine & Public Health, Madison. · University of Alabama at Birmingham. ·Arthritis Rheumatol · Pubmed #28881479.

ABSTRACT: -- No abstract --

3 Editorial Challenges in defining quality of care for glucocorticoid-induced osteoporosis: defending good against perfect. 2013

Saag, Kenneth G / Curtis, Jeffrey / Warriner, Amy. ·Division of Immunology and Rheumatology; ·J Rheumatol · Pubmed #24085752.

ABSTRACT: -- No abstract --

4 Review Pragmatic Clinical Trials in Osteoporosis. 2019

Adami, Giovanni / Saag, Kenneth G / Danila, Maria I. ·Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, 510 20th Street South, Faculty Office Tower 820D, Birmingham, AL, 35294, USA. · Rheumatology Unit, University of Verona, Pz Scuro 10, 37135, Verona, Italy. · Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, 510 20th Street South, Faculty Office Tower 820D, Birmingham, AL, 35294, USA. ksaag@uab.edu. ·Curr Osteoporos Rep · Pubmed #31773402.

ABSTRACT: PURPOSE OF REVIEW: In this review, we present the application of pragmatic clinical trials for evaluating interventions in osteoporosis, and we discuss methodological considerations for designing and conducting a pragmatic clinical trial compared with a classical randomized clinical trial. RECENT FINDINGS: Pragmatic clinical trials are a popular study design testing effectiveness of health interventions and are intended to address the limitations associated with traditional explanatory randomized clinical trials testing efficacy of interventions. To date, only few pragmatic clinical trials have been conducted in osteoporosis. Pragmatic clinical trials are conducted under routine clinical practice setting and are intended to inform policy makers and clinical decisions. Osteoporosis is a chronic disease well-suited to this particular study design given the existence of a clear and specific natural endpoint, namely fracture occurrence, and the availability of several treatments to prevent fractures.

5 Review Glucocorticoid-induced osteoporosis: from clinical trials to clinical practice. 2019

Adami, Giovanni / Rahn, Elizabeth J / Saag, Kenneth G. ·Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, 510 20th Street South, Faculty Office Tower 820D, Birmingham, AL 35294, USA. · Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA. ·Ther Adv Musculoskelet Dis · Pubmed #31565078.

ABSTRACT: Glucocorticoid-induced osteoporosis (GIOP) is the most common form of secondary osteoporosis. To date, six large randomized controlled clinical trials on the efficacy of pharmaceutical treatment in GIOP have been conducted. All of these studies have focused predominately on bone mineral density outcomes, and none of them have been statistically powered to address fracture endpoints. The purpose of this review is to highlight differences in the design and results within these large randomized GIOP clinical trials, and how these differences might affect clinical decisions. Differences between studies in trial design, populations studied, and variable efficacy impact the comparability and generalizability of these findings, and ultimately should affect practitioners' behavior. We review the clinical trials that provide the best quality evidence on comparative efficacy and safety of GIOP treatments. We also propose suggestions on the design of future GIOP clinical trials with attention to improved generalizability, and, ideally, study designs that might achieve fracture outcomes.

6 Review Osteoporosis Pathophysiology, Epidemiology, and Screening in Rheumatoid Arthritis. 2019

Adami, Giovanni / Saag, Kenneth G. ·Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, 510 20th Street South, Faculty Office Tower 820D, Birmingham, AL, 35294, USA. · Rheumatology Unit, University of Verona, Pz Scuro 10, 37135, Verona, Italy. · Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, 510 20th Street South, Faculty Office Tower 820D, Birmingham, AL, 35294, USA. ksaag@uabmc.edu. ·Curr Rheumatol Rep · Pubmed #31123839.

ABSTRACT: PURPOSE OF REVIEW: To review the burden of osteoporosis (OP) in rheumatoid arthritis (RA) and to describe the OP screening strategies applied in RA. RECENT FINDINGS: RA is an inflammatory condition that predisposes patients to development of OP. OP in RA has a multifactorial pathogenesis with systemic inflammation and glucocorticoid use playing major roles. Newer studies have reported an intriguing association between RA autoantibodies and the development of OP. OP screening strategies in RA patients include clinical and vitamin D assessment, biochemical markers of bone remodeling, and bone imaging evaluations, particularly dual-energy X-ray absorptiometry (DXA). Fragility fractures are an important comorbidity of RA. OP screening strategies are both feasible and effective in RA patients and recommended by most specialty organizations. Given the considerable exposure to factors related to OP development, such as pro-inflammatory cytokines and glucocorticoid treatment, special attention should be directed to biochemical and DXA results in RA patients.

7 Review Tools and Methods for Real-World Evidence Generation: Pragmatic Trials, Electronic Consent, and Data Linkages. 2019

Curtis, Jeffrey R / Foster, P Jeff / Saag, Kenneth G. ·Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: jcurtis@uab.edu. · Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA. ·Rheum Dis Clin North Am · Pubmed #30952398.

ABSTRACT: Real-world evidence requires use of new tools and methods to support efficient evidence generation. Among those tools are pragmatic trials, utilization of central/single institutional review board and electronic consent, and data linkages between diverse types of data sources (eg, a trial or registry to administrative claims or electronic medical record data). This article reviews these topics in the context of describing several exemplar use cases specific to rheumatology and provides perspective regarding both the promise and potential pitfalls in using these tools and approaches.

8 Review Glucocorticoid-induced osteoporosis: 2019 concise clinical review. 2019

Adami, G / Saag, K G. ·Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, 510 20th Street South, Faculty Office Tower 820D, Birmingham, AL, 35294, USA. · Rheumatology Unit, University of Verona, Pz Scuro 10, 37135, Verona, Italy. · Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, 510 20th Street South, Faculty Office Tower 820D, Birmingham, AL, 35294, USA. ksaag@uabmc.edu. ·Osteoporos Int · Pubmed #30805679.

ABSTRACT: Glucocorticoids remain widely used for many medical conditions, and fractures are the most serious common adverse event related to long-term glucocorticoid use. Glucocorticoid-induced osteoporosis (GIOP) develops in a time- and dose-dependent manner, but even at low doses, an increased risk of fragility fracture may be observed even within the first month of treatment. GIOP is mediated by multiple pathophysiologic mechanisms resulting in an inhibition of bone formation and an increase in bone resorption. The clinical assessment of GIOP has potential pitfalls since dual-energy X-ray absorptiometry (DXA) may underestimate the risk of fracture in patients treated with glucocorticoids. Many national organizations have developed guidelines for assessing fracture risk and treating patients with, or at risk for, GIOP. These groups advocate both antiresorptive agents and bone-forming agents based predominately on their efficacy in improving bone mineral density. Oral bisphosphonates are generally the first-line therapy for GIOP in most patients due to their proven efficacy, good safety, and low cost. For those patients at greater risk of fracture, teriparatide should be considered earlier, based on its ability to significantly reduce vertebral fractures when compared with alendronate. GIOP remains a major public health concern that is at least partially preventable with current and potential future therapeutic options.

9 Review Importance of Recent Fracture as Predictor of Imminent Fracture Risk. 2018

Schnell, Amanda D / Curtis, Jeffrey R / Saag, Kenneth G. ·Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, 510 20th Street South, Faculty Office Tower 820D, Birmingham, AL, 35294, USA. · Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, 510 20th Street South, Faculty Office Tower 820D, Birmingham, AL, 35294, USA. ksaag@uabmc.edu. ·Curr Osteoporos Rep · Pubmed #30368717.

ABSTRACT: PURPOSE OF REVIEW: To examine the importance of recent fracture as a predictor of imminent fracture risk, review the importance of prior fracture type and timing, and identify risk factors for recurrent osteoporotic fracture. RECENT FINDINGS: Prior fracture type and timing impact risk of subsequent fracture that is largely independent of bone mineral density. Site of re-fracture is similar to original major osteoporotic fracture. Incidence of recurrent major osteoporotic fracture is greatest within the first year. Other risk factors include those that pertain to individual characteristics. Approved osteoporosis therapies reduce risk of recurrent fracture. Prior fracture timing, type, and individual characteristics are important components of predicting the risk of future fracture. Initiation of osteoporosis medication therapy should be started after initial fracture to reduce the risk of future fracture, though these medications typically take 6-12 months to have an effect, during which time is the highest rate of imminent re-fracture.

10 Review Improving drug adherence in osteoporosis: an update on more recent studies. 2018

Jaleel, Ayesha / Saag, Kenneth G / Danila, Maria I. ·Brookwood Baptist Health, Birmingham, AL, USA. · University of Alabama at Birmingham, Birmingham, AL, USA. · University of Alabama at Birmingham, Faculty Office Tower, Room 838510 20th Street South, Birmingham, AL 35294-3408, USA. ·Ther Adv Musculoskelet Dis · Pubmed #30023009.

ABSTRACT: Similar to other chronic diseases such as diabetes and hypertension, osteoporosis has struggled with suboptimal medication adherence, resulting in an increased risk of fractures and all-cause mortality. The goal of this narrative review was to summarize interventions to improve medication adherence in osteoporosis. Because past reviews of this topic covered published literature through 2013, we conducted our literature search to include the period between January 2012 and November 2017. We identified 10 studies evaluating healthcare system and patient interventions aimed at improving osteoporosis treatment adherence, including three fracture liaison service (FLS) programs, one pharmacist-delivered counseling program, and six patient-directed interventions consisting of three coaching or counseling programs and three interventions using reminder prompts. Four out of the six patient-directed interventions did not lead to significant improvements in outcomes, suggesting that patient-directed interventions may have limited success in this setting. The healthcare system interventions that evaluated FLS programs and pharmacist-directed tailored counseling were effective at improving medication adherence; however, the studies were not randomized, they were costly, resource intensive and effective in countries with more centralized healthcare, possibly limiting their generalizability. In conclusion, while healthcare system interventions such as FLS, and pharmacist-delivered counseling appeared to be successful in improving osteoporosis medication adherence in some settings, behavioral interventions including patient counseling and reminder prompts for medication utilization were not, perhaps due to patient perceptions regarding osteoporosis consequences and need for treatment. Thus, these patient attributes may define patients 'at high risk' for poor adherence and developing intervention approaches to enhance patient knowledge and understanding of osteoporosis and its consequences may improve the perception of the need for treatment, optimize osteoporosis care and thereby improve overall outcomes of patients with osteoporosis. We hope that the knowledge gained through our review will help inform the design of further programs aimed at optimizing osteoporosis care.

11 Review Glucocorticoid-induced Osteoporosis. 2016

Whittier, Xena / Saag, Kenneth G. ·Division of Clinical Immunology and Rheumatology, 851 Faculty Office Tower, 510 20th Street South, Birmingham, AL 35294, USA. · Division of Clinical Immunology and Rheumatology, Department of Medicine, Center for Education and Research on Therapeutics (CERTs), Center for Outcomes, Effectiveness Research and Education (COERE), Center of Research Translation (CORT) in Gout and Hyperuricemia, University of Alabama at Birmingham, 820 Faculty Office Tower, 510 20th Street South, Birmingham, AL 35294, USA. Electronic address: ksaag@uab.edu. ·Rheum Dis Clin North Am · Pubmed #26611558.

ABSTRACT: Glucocorticoid-induced osteoporosis (GIOP) is one of the most common and serious adverse effects associated with glucocorticoid use. This article highlights GIOP pathophysiology, epidemiologic associations, effective treatment, and lifestyle modifications that can reduce fracture risk for long-term glucocorticoid users and additionally emphasizes the importance of early intervention.

12 Review Evaluating and mitigating fracture risk in established rheumatoid arthritis. 2015

Mullen, Matthew B / Saag, Kenneth G. ·University of Alabama-Birmingham, Birmingham, AL, USA. · University of Alabama-Birmingham, Birmingham, AL, USA. Electronic address: ksaag@uab.edu. ·Best Pract Res Clin Rheumatol · Pubmed #26697770.

ABSTRACT: Patients with rheumatoid arthritis are predisposed to systemic bone loss, and they are at an increased risk of fractures. Although there are similarities in the patient demographics between rheumatoid arthritis patients and the general population of osteoporosis patients, there are factors, particularly the use of glucocorticoids, which are specific to rheumatoid arthritis. These factors can lead to an increased risk of bone loss and fracture. Given that fractures are often very debilitating, especially in elderly patients, it is of paramount importance for the practicing rheumatologist to be aware of ways to reduce the risk of fracture in patients with rheumatoid arthritis. This review discusses currently available modalities for fracture risk assessment as well as pharmacologic and lifestyle interventions available to treat and prevent bone loss in rheumatoid arthritis patients.

13 Review Fracture mortality: associations with epidemiology and osteoporosis treatment. 2014

Sattui, Sebastian E / Saag, Kenneth G. ·Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, 820 Faculty Office Tower, 510 20th Street South, Birmingham, AL 35294, USA. ·Nat Rev Endocrinol · Pubmed #25091729.

ABSTRACT: The rates of incident osteoporotic fractures seem to be stabilizing; however, fragility fractures are still associated with considerable disability, costs and an increased risk of mortality, which is particularly the case for fractures of the hip and vertebra. Mortality is usually highest during the first year after fracture; however, a notably increased mortality risk might persist for several years after the event. In addition to its efficacy in the prevention of new and recurrent osteoporotic fractures, medical treatment has been associated with improved survival after osteoporotic fractures. Observational studies and randomized controlled clinical trials have reported increased survival in patients with a fracture who are treated with bisphosphonates. Rates of medical treatment in patients with osteoporosis remain low, and although the rationale for the putative increase in survival is unclear, this emerging evidence might help further justify the use of medical treatment after fracture. However, further work is needed before medical therapy for mortality prevention in patients with osteoporotic fractures is accepted.

14 Review Glucocorticoid-related bone changes from endogenous or exogenous glucocorticoids. 2013

Warriner, Amy H / Saag, Kenneth G. ·aDivision of Endocrinology, Metabolism and Diabetes bDivision of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, USA. ·Curr Opin Endocrinol Diabetes Obes · Pubmed #24468753.

ABSTRACT: PURPOSE OF REVIEW: Glucocorticoids have a negative impact on bone through direct effects on bone cells and indirect effects on calcium absorption. Here, recent findings regarding glucocorticoid-induced osteoporosis, bone changes in patients with endogenous glucocorticoid derangements, and treatment of steroid-induced bone disease are reviewed. RECENT FINDINGS: Although the majority of our understanding arises from the outcomes of patients treated with exogenous steroids, endogenous overproduction appears to be similarly destructive to bone, but these effects are reversible with cure of the underlying disease process. Additionally, there are bone changes that occur in diseases that interrupt adrenal glucocorticoid production, both in response to our inability to perfectly match glucocorticoid replacement and also related to the underlying disease process. More investigation is required to understand which patients with endogenous overproduction or underproduction of glucocorticoid would benefit from osteoporosis treatment. Better understood is the benefit that can be achieved with currently approved treatments for glucocorticoid-induced osteoporosis from exogenous steroids. With growing concern of long-term use of bisphosphonates, however, further investigation into the duration of use and use in certain populations, such as children and premenopausal women, is essential. SUMMARY: Glucocorticoid-induced osteoporosis is a complex disease that is becoming better understood through advances in the study of exogenous and endogenous glucocorticoid exposure. Further advancement of proper treatment and prevention is on the horizon.

15 Review Osteopenia: debates and dilemmas. 2013

Zhang, Jie / Morgan, Sarah L / Saag, Kenneth G. ·Department of Epidemiology, University of Alabama at Birmingham, 1665 University Blvd, Ryals 230K, Birmingham, AL, 35294, USA, jszhang@uab.edu. ·Curr Rheumatol Rep · Pubmed #24222198.

ABSTRACT: Whether or not to use pharmacologic agents for primary prevention of fracture among elderly men and women with osteopenia is debated by clinicians. In this review we provide an update to enable better understanding and characterization of this population, including the prevalence of osteopenia, transitioning from osteopenia to osteoporosis, and clinically applicable tools for fracture risk assessment. We also emphasize the very limited evidence of the benefits and risks of anti-osteoporotic agents for this population for primary fracture prevention, and the need for future studies to guide clinical practice.

16 Review Prevention and treatment of bone changes associated with exposure to glucocorticoids. 2013

Warriner, Amy H / Saag, Kenneth G. ·Division of Endocrinology, Metabolism and Diabetes, University of Alabama at Birmingham, 702 Faculty Office Tower, 510 20th Street South, Birmingham, AL, 35233, USA, warriner@uab.edu. ·Curr Osteoporos Rep · Pubmed #24097304.

ABSTRACT: Rheumatologic diseases are associated with a proinflammatory state, which is thought to lead to many of the bone changes seen in treatment-naive patients. However, glucocorticoids remain a common treatment option for rheumatologic diseases and are known to have a negative impact on bone through direct effects on bone cells and indirect effects on calcium absorption. Despite the anti-inflammatory effect of glucocorticoids, fracture risk rises within the first 3 months of treatment. As such, osteoporosis prevention and treatment needs to be considered in all patients started on chronic glucocorticoids (≥3 months of treatment). For very low risk patients, conservative management with non-pharmacologic strategies may be appropriate. For the moderate to high fracture risk patients treated with glucocorticoids, pharmacologic treatment with 1 of the 4 approved medications should be considered. The challenge of educating physicians and patients of the risks of glucocorticoid induced osteoporosis remain.

17 Review Study design considerations for a large simple trial of bisphosphonates. 2013

Wright, Nicole C / Warriner, Amy H / Saag, Kenneth G. ·Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. ncwright@uab.edu ·Curr Opin Rheumatol · Pubmed #23656714.

ABSTRACT: PURPOSE OF REVIEW: To evaluate design considerations for an osteoporosis large simple trial (LST). RECENT FINDINGS: There is a growing need for more comparative effectiveness studies in osteoporosis. However, the design of such studies is challenged by issues surrounding study design, choosing comparator therapies, participant and outcome selection, data acquisition and data analysis. SUMMARY: LSTs are real-world studies that can have high levels of generalizability, if designed properly. We propose novel approaches to LSTs focusing on some of the challenges associated with comparative effectiveness research in osteoporosis. In this review, we discuss these considerations in the context of bisphosphonate active comparator initiation and discontinuation trials, while presenting advantages and disadvantages of the various design aspects for such studies.

18 Review Osteoporosis diagnosis and medical treatment. 2013

Warriner, Amy H / Saag, Kenneth G. ·Division of Endocrinology, Metabolism and Diabetes, University of Alabama at Birmingham, Birmingham, AL 35233, USA. warriner@uab.edu ·Orthop Clin North Am · Pubmed #23544819.

ABSTRACT: Osteoporosis, the presence of either low bone mineral density or a history of a fragility fracture, is known to be associated with an increased risk of future fracture. Fracture prevention is possible through use of both nonpharmacologic and prescription treatments. Despite recent controversy regarding the safety of calcium supplementation and the appropriate dosing of calcium and vitamin D, calcium and vitamin D remain an important part of bone health. However, prescription osteoporosis treatments should be considered for those at higher risk for fracture, and there are currently several treatment options available.

19 Review From fracture risk prediction to evaluating fracture patterns: recent advances in the epidemiology of osteoporosis. 2012

Wright, Nicole C / Saag, Kenneth G. ·Department of Epidemiology, University of Alabama at Birmingham, 35294, USA. ncwright@uab.edu ·Curr Rheumatol Rep · Pubmed #22453874.

ABSTRACT: Understanding the factors associated with fracture is one of the main research objective of the osteoporosis epidemiology field. Tools such as FRAX have overall improved the ability of clinicians and researchers to identify individuals at high risk of fragility fractures. However, the performance of these tools in specific subpopulations needs further examination. We highlight recent studies that have shown under- or overestimation of fractures using FRAX in subpopulations, as well as recently proposed modifications to this important algorithm. We also discuss recent evaluations of secular trends in fracture incidence.

20 Review Long-term safety concerns of antiresorptive therapy. 2011

Zhang, Jie / Saag, Kenneth G / Curtis, Jeffrey R. ·Health Services/Comparative Effectiveness Research Training Program, Department of Epidemiology, University of Alabama at Birmingham, 1665 University Boulevard, RPHB 517B, Birmingham, AL 35294, USA. ·Rheum Dis Clin North Am · Pubmed #22023898.

ABSTRACT: Bisphosphonates reduce the risk of major osteoporotic fractures and are the most commonly used medications for the prevention and treatment of osteoporosis. Although these medications are well tolerated and safe during large-scale clinical trials, several rare and serious adverse events are suspected to be associated with long-term bisphosphonate use. These adverse events include osteonecrosis of the jaw, atypical fractures, and esophageal cancer. This review summarizes studies examining the association between bisphosphonate use and these adverse outcomes, with a focus on large case series and controlled epidemiologic studies.

21 Review Potential and pitfalls of using large administrative claims data to study the safety of osteoporosis therapies. 2011

Zhang, Jie / Yun, Huifeng / Wright, Nicole C / Kilgore, Meredith / Saag, Kenneth G / Delzell, Elizabeth. ·Department of Epidemiology and Health Services/Comparative Effectiveness Research Training Program, University of Alabama at Birmingham, 1665 University Boulevard, RPHB 517B, Birmingham, AL 35294, USA jszhang@uab.edu ·Curr Rheumatol Rep · Pubmed #21312073.

ABSTRACT: Long-term bisphosphonate use may be associated with several rare adverse events. Such associations are not optimally evaluated in conventional randomized controlled trials due to the requirements of large numbers of patients and long-term follow-up. Alternatively, administrative claims data from various sources such as Medicare have been used. Because claims data are collected for billing and reimbursement purposes, they have limitations, including uncertain diagnostic validity and lack of detailed clinical information. Using such data for pharmacoepidemiologic research requires complex methodologies that may be less familiar to many researchers and clinicians. In this review, we discuss the strengths and limitations of using claims data for osteoporosis drug safety research, summarize recent advancements in methodologies that may be used to address the limitations, and present directions for future research using claims data.

22 Review American College of Rheumatology 2010 recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. 2010

Grossman, Jennifer M / Gordon, Rebecca / Ranganath, Veena K / Deal, Chad / Caplan, Liron / Chen, Weiling / Curtis, Jeffrey R / Furst, Daniel E / McMahon, Maureen / Patkar, Nivedita M / Volkmann, Elizabeth / Saag, Kenneth G. ·University of California, Los Angeles, 90095, USA. jgrossman@mednet.ucla.edu ·Arthritis Care Res (Hoboken) · Pubmed #20662044.

ABSTRACT: -- No abstract --

23 Review From bone biology to clinical outcome: state of the art and future perspectives. 2010

Schett, Georg / Saag, Kenneth G / Bijlsma, Johannes W J. ·Department of Internal Medicine 3, Erlangen, Germany. ·Ann Rheum Dis · Pubmed #20650876.

ABSTRACT: In the last decade progress has been made in our understanding of bone biology. In particular, the relation between inflammation and bone has become much clearer, leading to bone-targeting therapies in inflammatory rheumatic diseases. The clinical sequelae of the influences of both inflammation and immobility (due to arthritis) on bone for different rheumatic diseases (such as rheumatoid arthritis, systemic lupus erythematosus and spondyloarthritides) have also now captured the attention of clinicians. In the last decade the well-known negative influences of glucocorticoids on bone have become more treatable as a result of new drugs that stimulate osteoblasts and restore the negative bone balance.

24 Clinical Trial Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis. 2017

Saag, Kenneth G / Petersen, Jeffrey / Brandi, Maria Luisa / Karaplis, Andrew C / Lorentzon, Mattias / Thomas, Thierry / Maddox, Judy / Fan, Michelle / Meisner, Paul D / Grauer, Andreas. ·From the University of Alabama, Birmingham (K.G.S.) · Amgen, Thousand Oaks, CA (J.P., J.M., M.F., A.G.) · University of Florence, Florence, Italy (M.L.B.) · McGill University, Montreal (A.C.K.) · University of Gothenburg and Sahlgrenska University Hospital, Mölndal, Sweden (M.L.) · Centre Hospitalier Universitaire de Saint-Étienne, Saint-Étienne, France (T.T.) · and UCB Pharma, Brussels (P.D.M.). ·N Engl J Med · Pubmed #28892457.

ABSTRACT: BACKGROUND: Romosozumab is a monoclonal antibody that binds to and inhibits sclerostin, increases bone formation, and decreases bone resorption. METHODS: We enrolled 4093 postmenopausal women with osteoporosis and a fragility fracture and randomly assigned them in a 1:1 ratio to receive monthly subcutaneous romosozumab (210 mg) or weekly oral alendronate (70 mg) in a blinded fashion for 12 months, followed by open-label alendronate in both groups. The primary end points were the cumulative incidence of new vertebral fracture at 24 months and the cumulative incidence of clinical fracture (nonvertebral and symptomatic vertebral fracture) at the time of the primary analysis (after clinical fractures had been confirmed in ≥330 patients). Secondary end points included the incidences of nonvertebral and hip fracture at the time of the primary analysis. Serious cardiovascular adverse events, osteonecrosis of the jaw, and atypical femoral fractures were adjudicated. RESULTS: Over a period of 24 months, a 48% lower risk of new vertebral fractures was observed in the romosozumab-to-alendronate group (6.2% [127 of 2046 patients]) than in the alendronate-to-alendronate group (11.9% [243 of 2047 patients]) (P<0.001). Clinical fractures occurred in 198 of 2046 patients (9.7%) in the romosozumab-to-alendronate group versus 266 of 2047 patients (13.0%) in the alendronate-to-alendronate group, representing a 27% lower risk with romosozumab (P<0.001). The risk of nonvertebral fractures was lower by 19% in the romosozumab-to-alendronate group than in the alendronate-to-alendronate group (178 of 2046 patients [8.7%] vs. 217 of 2047 patients [10.6%]; P=0.04), and the risk of hip fracture was lower by 38% (41 of 2046 patients [2.0%] vs. 66 of 2047 patients [3.2%]; P=0.02). Overall adverse events and serious adverse events were balanced between the two groups. During year 1, positively adjudicated serious cardiovascular adverse events were observed more often with romosozumab than with alendronate (50 of 2040 patients [2.5%] vs. 38 of 2014 patients [1.9%]). During the open-label alendronate period, adjudicated events of osteonecrosis of the jaw (1 event each in the romosozumab-to-alendronate and alendronate-to-alendronate groups) and atypical femoral fracture (2 events and 4 events, respectively) were observed. CONCLUSIONS: In postmenopausal women with osteoporosis who were at high risk for fracture, romosozumab treatment for 12 months followed by alendronate resulted in a significantly lower risk of fracture than alendronate alone. (Funded by Amgen and others; ARCH ClinicalTrials.gov number, NCT01631214 .).

25 Clinical Trial Relationship of weight, height, and body mass index with fracture risk at different sites in postmenopausal women: the Global Longitudinal study of Osteoporosis in Women (GLOW). 2014

Compston, Juliet E / Flahive, Julie / Hosmer, David W / Watts, Nelson B / Siris, Ethel S / Silverman, Stuart / Saag, Kenneth G / Roux, Christian / Rossini, Maurizio / Pfeilschifter, Johannes / Nieves, Jeri W / Netelenbos, J Coen / March, Lyn / LaCroix, Andrea Z / Hooven, Frederick H / Greenspan, Susan L / Gehlbach, Stephen H / Díez-Pérez, Adolfo / Cooper, Cyrus / Chapurlat, Roland D / Boonen, Steven / Anderson, Frederick A / Adami, Silvano / Adachi, Jonathan D / Anonymous4090764. ·Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge, UK. ·J Bone Miner Res · Pubmed #23873741.

ABSTRACT: Low body mass index (BMI) is a well-established risk factor for fracture in postmenopausal women. Height and obesity have also been associated with increased fracture risk at some sites. We investigated the relationships of weight, BMI, and height with incident clinical fracture in a practice-based cohort of postmenopausal women participating in the Global Longitudinal study of Osteoporosis in Women (GLOW). Data were collected at baseline and at 1, 2, and 3 years. For hip, spine, wrist, pelvis, rib, upper arm/shoulder, clavicle, ankle, lower leg, and upper leg fractures, we modeled the time to incident self-reported fracture over a 3-year period using the Cox proportional hazards model and fitted the best linear or nonlinear models containing height, weight, and BMI. Of 52,939 women, 3628 (6.9%) reported an incident clinical fracture during the 3-year follow-up period. Linear BMI showed a significant inverse association with hip, clinical spine, and wrist fractures: adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) per increase of 5 kg/m(2) were 0.80 (0.71-0.90), 0.83 (0.76-0.92), and 0.88 (0.83-0.94), respectively (all p < 0.001). For ankle fractures, linear weight showed a significant positive association: adjusted HR per 5-kg increase 1.05 (1.02-1.07) (p < 0.001). For upper arm/shoulder and clavicle fractures, only linear height was significantly associated: adjusted HRs per 10-cm increase were 0.85 (0.75-0.97) (p = 0.02) and 0.73 (0.57-0.92) (p = 0.009), respectively. For pelvic and rib fractures, the best models were for nonlinear BMI or weight (p = 0.05 and 0.03, respectively), with inverse associations at low BMI/body weight and positive associations at high values. These data demonstrate that the relationships between fracture and weight, BMI, and height are site-specific. The different associations may be mediated, at least in part, by effects on bone mineral density, bone structure and geometry, and patterns of falling.

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