scholarly journals NIH PATHWAYS TO PREVENTION WORKSHOP: RESEARCH GAPS FOR LONG-TERM DRUG THERAPIES FOR FRACTURE PREVENTION

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S748-S748
Author(s):  
Lyndon Joseph ◽  
Faye Chen
Keyword(s):  
Medical Condition ◽  
Scientific Evidence ◽  
Femoral Fractures ◽  
Osteoporotic Fractures ◽  
Fracture Prevention ◽  
Osteonecrosis Of The Jaw ◽  
Drug Discontinuation ◽  
Serious Adverse Events ◽  
The Impact

Abstract The NIH Pathways to Prevention Workshop was held on October 30-31, 2018 to present scientific evidence, as well as physician and patient perspectives to better understand the benefits and harms of drug therapies for osteoporosis fracture prevention. Osteoporotic fractures lead to substantial morbidity, mortality, and economic costs. The underlying medical condition, is a skeletal disorder characterized by compromised bone strength predisposing to increased fracture risk. Several medications approved by the U.S. Food and Drug Administration to prevent osteoporotic fractures have been effective when taken by people who are at high risk of fracture. These include bisphosphonates , denosumab, teriparatide, estrogens, and selective estrogen-receptor modulators. However, rare but serious adverse events, such as atypical femoral fractures and osteonecrosis of the jaw associated with bisphosphonates have raised questions regarding the safety of their use. There is limited evidence on the benefits and harms of long-term osteoporosis drug therapy, including the timing and duration of drug discontinuation or drug holidays. It is not clearly known which patients will benefit or may be harmed from continued drug intervention, who should and should not be put on drug holiday, how to identify such patients and properly treat them, and how to predict their outcomes. Key scientific areas covered by the workshop included: the benefits and risks of osteoporotic drugs with short-term and long-term use and factors that influence outcomes; the impact of drug discontinuation and drug holidays on outcomes; and patient and clinician factors that impact the use of and adherence to osteoporotic drugs.

scholarly journals Fraturas Atípicas do Fémur Associadas a Terapêutica Prolongada com Bisfosfonatos

2013 ◽  
Vol 26 (6) ◽  
pp. 746
Author(s):  
Francisco Flores Santos ◽  
José Pinheiro da Silva ◽  
Paulo Felicíssimo
Keyword(s):  
Femoral Fracture ◽  
Scientific Evidence ◽  
Femoral Fractures ◽  
Osteoporotic Fractures ◽  
Femoral Shaft ◽  
Term Treatment ◽  
Atypical Femoral Fractures ◽  
Long Term Treatment

Introduction: Long-term treatment with bisphosphonates has been associated to atypical femoral fractures whose features are now clearly defined.Clinical Cases: We present two cases of female patients under bisphosphonate treatment for over 10 years who were admitted to our institution for subtrochanteric and femoral shaft fractures after low-energy trauma. They presented, respectively, a transverse and a short oblique femoral fracture, with thickening of the lateral cortex. They underwent surgical treatment obtaining good functional and imaging result.Discussion: These cases fulfill the established criteria for atypical femoral fracture, thereby illustrating a serious adverse event of long-term treatment with bisphosphonates. Such relationship has still not been clearly established by scientific evidence. However, its effectiveness in preventing osteoporotic fractures is well proven.Conclusion: The atypical femoral fractures are possibly a serious adverse effect of the long-term treatment with bisphosphonates. Scientific evidence still supports its use, however, the physician must be aware of these events and closely follow-up these patients.

scholarly journals Duration of Bisphosphonate Drug Holidays in Osteoporosis Patients: A Narrative Review of the Evidence and Considerations for Decision-Making

2021 ◽  
Vol 10 (5) ◽  
pp. 1140
Author(s):  
Kaleen N. Hayes ◽  
Elizabeth M. Winter ◽  
Suzanne M. Cadarette ◽  
Andrea M. Burden
Keyword(s):  
Surrogate Marker ◽  
Femoral Fractures ◽  
Osteonecrosis Of The Jaw ◽  
Bisphosphonate Therapy ◽  
Narrative Review ◽  
Drug Holiday ◽  
Future Research ◽  
Mineral Density ◽  
First Line Therapy

Bisphosphonates are first-line therapy for osteoporosis, with alendronate, risedronate, and zoledronate as the main treatments used globally. After one year of therapy, bisphosphonates are retained in bone for extended periods with extended anti-fracture effects after discontinuation. Due to this continued fracture protection and the potential for rare adverse events associated with long-term use (atypical femoral fractures and osteonecrosis of the jaw), a drug holiday of two to three years is recommended for most patients after long-term bisphosphonate therapy. The recommendation for a drug holiday up to three years is derived primarily from extensions of pivotal trials with alendronate and zoledronate and select surrogate marker studies. However, certain factors may modify the duration of bisphosphonate effects on a drug holiday and warrant consideration when determining an appropriate time off-therapy. In this narrative review, we recall what is currently known about drug holidays and discuss what we believe to be the primary considerations and areas for future research regarding drug holiday duration: total bisphosphonate exposure, type of bisphosphonate used, bone mineral density and falls risk, and patient sex and body weight.

Medication-Induced Musculoskeletal Changes

2019 ◽  
pp. 322-326
Author(s):  
Winnie A. Mar
Keyword(s):  
Musculoskeletal System ◽  
Gold Standard ◽  
Imaging Modality ◽  
Femoral Fractures ◽  
Osteonecrosis Of The Jaw ◽  
Bisphosphonate Therapy ◽  
Atypical Femoral Fractures ◽  
Osteoblastic Activity ◽  
Induced Changes

Chapter 117 discusses common medication-induced changes of the musculoskeletal system. The effect of corticosteroids on the musculoskeletal system, including osteoporosis and osteonecrosis, is discussed. Corticosteroids decrease osteoblastic activity, stimulate bone resorption, and decrease intestinal absorption of calcium. Complications of bisphosphonate therapy such as atypical femoral fractures and osteonecrosis of the jaw are reviewed. Myopathies and tendon pathologies are briefly discussed, as well as bony changes potentially seen with long-term voriconazole treatment. For osteoporosis, DXA scan is the gold standard, whereas radiography is usually the first imaging modality performed in patients on voriconazole therapy who present with pain.

scholarly journals Survival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving Nivolumab

2014 ◽  
Vol 32 (10) ◽  
pp. 1020-1030 ◽  
Author(s):  
Suzanne L. Topalian ◽  
Mario Sznol ◽  
David F. McDermott ◽  
Harriet M. Kluger ◽  
Richard D. Carvajal ◽  
...  
Keyword(s):  
Overall Survival ◽  
Randomized Clinical Trials ◽  
Objective Response ◽  
Response Duration ◽  
Advanced Melanoma ◽  
Immune Memory ◽  
Drug Discontinuation ◽  
Median Response ◽  
The Impact

PurposeProgrammed cell death 1 (PD-1) is an inhibitory receptor expressed by activated T cells that downmodulates effector functions and limits the generation of immune memory. PD-1 blockade can mediate tumor regression in a substantial proportion of patients with melanoma, but it is not known whether this is associated with extended survival or maintenance of response after treatment is discontinued.Patients and MethodsPatients with advanced melanoma (N = 107) enrolled between 2008 and 2012 received intravenous nivolumab in an outpatient setting every 2 weeks for up to 96 weeks and were observed for overall survival, long-term safety, and response duration after treatment discontinuation.ResultsMedian overall survival in nivolumab-treated patients (62% with two to five prior systemic therapies) was 16.8 months, and 1- and 2-year survival rates were 62% and 43%, respectively. Among 33 patients with objective tumor regressions (31%), the Kaplan-Meier estimated median response duration was 2 years. Seventeen patients discontinued therapy for reasons other than disease progression, and 12 (71%) of 17 maintained responses off-therapy for at least 16 weeks (range, 16 to 56+ weeks). Objective response and toxicity rates were similar to those reported previously; in an extended analysis of all 306 patients treated on this trial (including those with other cancer types), exposure-adjusted toxicity rates were not cumulative.ConclusionOverall survival following nivolumab treatment in patients with advanced treatment–refractory melanoma compares favorably with that in literature studies of similar patient populations. Responses were durable and persisted after drug discontinuation. Long-term safety was acceptable. Ongoing randomized clinical trials will further assess the impact of nivolumab therapy on overall survival in patients with metastatic melanoma.

scholarly journals Do bisphosphonate-related atypical femoral fractures and osteonecrosis of the jaw affect the same group of patients? A pilot study

2014 ◽  
Vol 6 (1) ◽  
Author(s):  
Haitham Afif ◽  
Sebastian Mukka ◽  
Göran Sjödén ◽  
Arkan S. Sayed-Noor
Keyword(s):  
Clinical Practice ◽  
Pilot Study ◽  
Femoral Fractures ◽  
Osteonecrosis Of The Jaw ◽  
Simultaneous Occurrence ◽  
Limited Sample ◽  
Atypical Femoral Fractures ◽  
Limited Sample Size ◽  
Dental Records

Bisphosphonates (BPs) are commonly used drugs in clinical practice. In this pilot study, we investigated whether bisphosphonate-related atypical femoral fractures (AFF) and osteonecrosis of the jaw (ONJ) occurred simultaneously in the same group of patients. Six ONJ patients were examined by an orthopedic surgeon and 5 AFF patients were examined by a dentist to look for manifestations of simultaneous occurrence of AFF in ONJ patients and <em>vice versa</em>. The required radiological investigations and previous medical and dental records were available. No simultaneous occurrence of AFF and ONJ was found in the examined patients. In this pilot study with limited sample size, no manifestations of simultaneous occurrence of AFF and ONJ were found. This could be an indication that these complications have different pathophysiologies and affect different subgroups of patients on long-term BP treatment.

scholarly journals Morbilidade Neonatal na Diabetes Gestacional: Coincidência ou Consequência do Consenso de 2011

2017 ◽  
Vol 30 (9) ◽  
pp. 589
Author(s):  
Gabriela Mimoso ◽  
Guiomar Oliveira
Keyword(s):  
Gestational Diabetes ◽  
Scientific Evidence ◽  
Neonatal Morbidity ◽  
Diabetes Diagnosis ◽  
Perinatal Complications ◽  
Before And After ◽  
Short And Long Term ◽  
New Guidelines ◽  
The Impact

Introduction: Gestational diabetes is one of the diseases associated with pregnancy with higher rate of complications. Despite being a transitory condition, short and long term complications related to gestational diabetes have been described. There is scientific evidence to say that good metabolic control decreases perinatal complications. In 2011, new criteria was proposed for its diagnosis, which made possible its diagnosis during the 1st trimester of pregnancy. The aim of this study is to compare neonatal morbidity in two groups of women with gestational diabetes diagnosis before and after the latest Portuguese guidelines for diabetes and pregnancy were published (February 2011).Material and Methods: We included all newborns born in Maternidade Bissaya Barreto whose mother, followed at our maternity between 2008 and 2013, had unifetal pregnancy complicated by diabetes. We used a perinatal database and analysed the impact of the new guidelines in perinatal morbidity over two periods of three years.Results: There were 774 women who met the inclusion criteria. We found that gestational diabetes was diagnosed earlier, insulin therapy was more frequent. Neonatal morbidity was increased, and there were more cases of neonatal hypoglycemia and congenital anomalies, and newborns became smaller for gestational age.Discussion: The increase in neonatal morbidity was associated with early diagnosis and rigorous metabolic control.Conclusion: To analyse national data will be fundamental to understand this unexpected increase in morbidity.

Sociodemographic Factors Predict Medical Conditions Among Five-Year Survivors of Adolescent and Young Adult Hodgkin Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 693-693
Author(s):  
Theresa Keegan ◽  
Qian Li ◽  
Amy Steele ◽  
Elysia Alvarez ◽  
Ann M Brunson ◽  
...  
Keyword(s):  
Research Funding ◽  
Medical Condition ◽  
Circulatory System ◽  
Sociodemographic Factors ◽  
Medical Conditions ◽  
Second Cancers ◽  
Race Ethnicity ◽  
Asian Pacific ◽  
The Impact

Abstract Introduction: Survivors of Hodgkin lymphoma (HL) experience high risks of second cancers and cardiovascular disease. However, few population-based studies have focused on these risks in adolescents and young adults (AYAs) and none have considered whether the occurrence of these and other medical conditions differ by sociodemographic factors in long-term AYA HL survivors. Methods: Data for 5,667 patients aged 15-39 when diagnosed with HL during 1988-2007 and surviving a minimum of 5 years from diagnosis were obtained from the California Cancer Registry and followed in California hospital, emergency department and ambulatory surgery discharge databases. Discharge diagnoses were categorized to classify medical conditions as hypothyroidism, or infectious, blood, nervous, respiratory, and circulatory system conditions. Second cancers were obtained from the cancer registry. We estimated the cumulative incidence of developing each medical condition ≥ 5 years after diagnosis, accounting for death as a competing risk, stratified by race/ethnicity, neighborhood socioeconomic status (SES) at diagnosis, and health insurance status at diagnosis/initial treatment (available from 1996-2012). We examined the impact of these baseline sociodemographic characteristics on the occurrence of medical conditions using multivariable logistic regression and the impact of medical conditions on mortality using multivariable Cox proportional hazards regression with medical conditions as time-dependent covariates. Results are presented as adjusted odds ratios (OR) or hazard ratios (HR) with 95% confidence intervals (CI). Results: Forty-eight percent (n=2,710) of AYAs experienced one medical condition and 31% (n=1,718) had two or more medical conditions ≥ 5 years from HL diagnosis. AYAs survivors with public or no insurance (vs private) had a greater likelihood of experiencing all medical conditions, except second cancers and hypothyroidism (Table). More than 27% of AYAs with public or no insurance (vs private) experienced infectious (28% vs 14%), blood (28% vs 19%), respiratory (39% vs 26%) and circulatory system (34% vs 24%) conditions at 15-years after diagnosis. Compared to non-Hispanic Whites, blacks had a higher likelihood of all medical conditions except second cancers and hypothyroidism; Asian/Pacific Islanders had a higher likelihood of circulatory system diseases (Table). The incidence of infectious (23%), blood (30%), respiratory (36%) and circulatory system (35%) conditions were significantly higher among Black AYA HL survivors at 15-years than AYAs of other race/ethnicities (all p values <0.001). Consistent with the multivariable logistic regression analyses (Table), AYAs residing in low (vs high) SES neighborhoods had a higher incidence of infectious (18% vs 12%), blood (21% vs 15%), respiratory (27% vs 20%) and circulatory system (23% vs 18%) conditions at 15-years after diagnosis (all p values <0.001). The risk of death was increased among AYAs with blood conditions (HR=4.73, CI: 3.59-6.23), respiratory conditions (HR=3.73, CI: 2.87-4.85), infectious conditions (HR=3.11, CI: 2.43-3.99), subsequent cancers (HR=3.03, CI: 2.40-3.82) and circulatory system conditions (HR=2.85, CI: 2.24-3.61). Conclusion: This study found that 5-year AYA HL survivors who were uninsured or publicly insured, of Black or Asian/Pacific Islander race/ethnicity, or who resided in lower SES neighborhoods were at higher risk for developing late medical conditions and mortality. Lack of access to preventive care and long-term surveillance associated with low SES and lack of health insurance may explain these findings. Survivorship programs should target these more vulnerable populations and these conditions to improve patient outcomes. Disclosures Flowers: AbbVie: Research Funding; Genentech: Consultancy, Research Funding; Infinity: Research Funding; NIH: Research Funding; ECOG: Research Funding; Mayo Clinic: Research Funding; Roche: Consultancy, Research Funding; Millenium/Takeda: Research Funding; Gilead: Consultancy, Research Funding; TG Therapeutics: Research Funding; Acerta: Research Funding; Pharmacyclics, LLC, an AbbVie Company: Research Funding.

scholarly journals The burden of osteoporosis in Brazil

2014 ◽  
Vol 58 (5) ◽  
pp. 434-443 ◽  
Author(s):  
Bruna Coelho Galvão Marinho ◽  
Luiza Paulino Guerra ◽  
Juliana Beaudette Drummond ◽  
Barbara C. Silva ◽  
Maria Marta Sarquis Soares
Keyword(s):  
Cost Effectiveness ◽  
Financial Burden ◽  
Scientific Evidence ◽  
Treatment Strategies ◽  
Indirect Costs ◽  
Osteoporotic Fractures ◽  
Fragility Fractures ◽  
Treatment Of Osteoporosis ◽  
The Cost ◽  
The Impact

Osteoporotic fractures impose severe physical, psychosocial, and financial burden both to the patient and the society. Studies on the prevalence of osteoporosis and fragility fractures in Brazil show a wide variation, due to differences in sample size, the population studied, and methodologies. Few studies have been conducted in Brazil about the cost-effectiveness analyses of different intervention options aimed at the diagnosis and treatment of osteoporosis. Investigation and treatment strategies based on cost-effectiveness and scientific evidence are essential in the preparation of public health policies with the ultimate goal of reducing the incidence of fractures and, consequently, the direct and indirect costs associated with them. This article reviews the Brazilian burden of osteoporosis in terms of the prevalence and fractures attributable to the disease, the costs related to the investigation and management, as well as the impact of osteoporosis on the population as a whole and on affected individuals.

Treatment of Bisphosphonate-Related Osteonecrosis of the Jaw With Plasma Rich in Growth Factors After Dental Implant Surgery: A Case Report

2019 ◽  
Vol 45 (4) ◽  
pp. 289-296 ◽  
Author(s):  
Ignacio García Gil ◽  
Barbara Molina Ponte ◽  
Sergio Trapote Mateo ◽  
Jaime Jiménez García
Keyword(s):  
Growth Factors ◽  
Dental Implants ◽  
Dental Implant ◽  
Clinical Case ◽  
Scientific Evidence ◽  
Osteonecrosis Of The Jaw ◽  
Oral Bisphosphonates ◽  
Implant Surgery ◽  
Dental Implant Surgery

Oral bisphosphonates are commonly used to improve bone density in patients who suffer from a variety of pathologies. However, they have also been known to cause bisphosphonate-related osteonecrosis of the jaws (BRONJ). The aim of this clinical case presentation is to (1) determine whether the currently recommended length of time that oral bisphosphonates should be discontinued, before performing dental implant surgery, is sufficient to prevent BRONJ and (2) to describe an alternative treatment for BRONJ. A 65-year-old female patient developed BRONJ after receiving mandibular dental implants 5 months after discontinuing alendronic acid (Fosamax). The BRONJ was treated by surgical osteotomy and plasma rich in growth factors (PRGF), and the patient was followed up with biweekly examinations, which included 0.2% chlorhexidine mouthwashes and removal of any remaining necrotic bone. The dental implants were loaded 41 weeks after surgery and followed up with periapical radiographs and implant stability quotient measurements at 3, 6, 12, and 24 months postloading. Although the Association of Oral and Maxillofacial Surgeons protocols for suspension of presurgical oral bisphosphonates were followed, this patient still developed BRONJ after implant surgery. While a multitude of treatments have been described in the literature, there is not enough scientific evidence to support any one treatment. Based on this clinical case, it can be concluded that the potential adverse effects of oral bisphosphonates on the jaws could be greater than expected and that treatment with PRGF produces promising results, although more long-term studies are necessary to confirm these findings.

An English “like no other”?: Language Contact and Change in Quebec

2006 ◽  
Vol 51 (2-3) ◽  
pp. 185-213 ◽  
Author(s):  
Shana Poplack ◽  
James A. Walker ◽  
Rebecca Malcolmson
Keyword(s):  
Language Contact ◽  
Language Change ◽  
Scientific Evidence ◽  
Minority Language ◽  
Empirical Measure ◽  
The Impact ◽  
Language Contact And Change

AbstractAlthough the received wisdom is that English in Quebec, as a minority language, has undergone contact-induced language change, little scientific evidence has been brought to bear on this claim. We describe a project designed to assess the impact of a majority language on the structure of the minority language in a situation of long-term contact. The existence and directionality of change is assessed by comparing the behaviour of linguistic phenomena (1) over (apparent) time, (2) according to intensity of contact, and (3) against French as a non-contact benchmark and putative source. We detail the methods employed in selecting a sample and constituting a corpus, and characterize the speakers and aspects of their speech. Finally, we present an analysis of the sociolinguistic situation of the Quebec anglophone community, and offer an empirical measure of the impact of the French lexicon on Quebec English.

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