Predicting Fracture Risk in Younger Postmenopausal Women: Comparison of the Garvan and FRAX Risk Calculators in the Women's Health Initiative Study.

BACKGROUND: Guidelines recommend fracture risk assessment in postmenopausal women aged 50-64, but the optimal method is unknown. OBJECTIVES: To compare discrimination and calibration of the Fracture Risk Assessment Tool (FRAX) and Garvan fracture risk calculator for predicting fractures in postmenopausal women aged 50-64 at baseline. DESIGN: Prospective observational study. PARTICIPANTS: Sixty-three thousand seven hundred twenty-three postmenopausal women aged 50-64 years participating in the Women's Health Initiative Observational Study and Clinical Trials. MAIN MEASURES: Incident hip fractures and major osteoporotic fractures (MOF) during 10-year follow-up. Calculated FRAX- and Garvan-predicted hip fracture and MOF fracture probabilities. KEY RESULTS: The observed 10-year hip fracture probability was 0.3% for women aged 50-54 years (n = 14,768), 0.6% for women aged 55-59 years (n = 22,442), and 1.1% for women aged 60-64 years (n = 25,513). At sensitivity thresholds ≥ 80%, specificity of both tools for detecting incident hip fracture during 10 years of follow-up was low: Garvan 30.6% (95% confidence interval [CI] 30.3-31.0%) and FRAX 43.1% (95% CI 42.7-43.5%). At maximal area under the receiver operating characteristic curve (AUC(c), 0.58 for Garvan, 0.65 for FRAX), sensitivity was 16.0% (95% CI 12.7-19.4%) for Garvan and 59.2% (95% CI 54.7-63.7%) for FRAX. At AUC(c) values, sensitivity was lower in African American and Hispanic women than among white women and lower in women aged 50-54 than those 60-64 years old. Observed hip fracture probabilities were similar to FRAX-predicted probabilities but greater than Garvan-predicted probabilities. At AUC(c) values (0.56 for both tools), sensitivity for identifying MOF was also low (range 26.7-46.8%). At AUC(c) values (0.55 for both tools), sensitivity for identifying any clinical fracture ranged from 18.1 to 34.0%. CONCLUSIONS: In postmenopausal women aged 50-64 years, the FRAX and Garvan fracture risk calculator discriminate poorly between women who do and do not experience fracture during 10-year follow-up. There is no useful threshold for either tool.

Malnutrition in Older Adults with Cancer.

PURPOSE OF REVIEW: Malnutrition is a common and under-recognized geriatric condition in older adults with cancer. This review describes the public health burden, malnutrition prevention, and the relationship among cancer cachexia, malnutrition, and sarcopenia. Finally, clinical practice recommendations on malnutrition and prevention are presented. RECENT FINDINGS: Advanced age and cancer stage, frailty, dementia, major depression, functional impairment, and physical performance are important risk factors for malnutrition in older adults with cancer. The Mini Nutrition Assessment (MNA), Malnutrition Universal Screening Tool (MUST), and Patient Generated Subjective Global Assessment (PG-SGA) are the most commonly used assessment tools in older adults with cancer. In addition, malnutrition is independently associated with poor overall survival and quality of life, longer hospital stays, greater hospital cost, and hospital readmission. Comprehensive malnutrition prevention is required for improving the nutrition status among older adults with cancer.

Fractures frequently occur in older cancer patients: the MD Anderson Cancer Center experience.

PURPOSE AND INTRODUCTION: A growing number of cancer patients are older adults aged 65 years and older. Patients with cancer are at increased risk for developing osteoporosis, falls, and fractures. We sought to identify the incidence of fractures in older adults who underwent cancer care between January 2013 and December 2015. METHODS: A comprehensive geriatric assessment was performed, and bone densitometry was measured at baseline, with a 2-year follow-up. RESULTS: In this study, among 304 patients with gastrointestinal, urologic, breast, lung, and gynecologic cancers we evaluated, and who completed the bone density testing (n = 199), 80% had osteoporosis or low bone mass (osteopenia). There was a higher prevalence of osteoporosis in cancer patients (40 vs. 16%, p = 0.05) than in population studies. Vitamin D insufficiency (< 30 ng/ml) was identified in 49% of tested cases (n = 245). Risk factors for low bone mass or osteoporosis were advanced age (p = 0.05), malnutrition (p = 0.04), and frailty (p = 0.01). Over the following 2 years (median follow-up 18 months), there was an incidence of fractures of 110 per 1000 person-years, or 2.8 times higher than reported in individuals without cancer. Risk factors for fractures included advanced age (70-79 vs. 60-69 years, p = 0.05) and frailty (p = 0.03). CONCLUSION: Most older cancer patients studied have osteoporosis or low bone mass, resulting in an almost 3-fold increase in fracture risk as compared to epidemiologic studies. Bone health issues are commonly seen in older cancer patients, we recommend universal bone density testing. The initiation of antiresorptive treatment when findings are of osteopenia or osteoporosis will reduce the risk of fractures.

Poor prognosis of patients with triple-negative breast cancer can be stratified by RANK and RANKL dual expression.

PURPOSE: As clinical studies have correlated RANK expression levels with survival in breast cancer, and that RANK signaling is dependent on its cognate ligand RANKL, we hypothesized that dual protein expression further stratifies the poor outcome in TNBC. METHODS: RANK mRNA and protein expression was evaluated in TNBC using genomic databases, cell lines and in a tissue microarray of curated primary tumor samples derived from 87 patients with TNBC. RANK expression was evaluated either by Mann-Whitney U test on log-normalized gene expression data or by Student's t test on FACS data. Analysis of RANK and RANKL immunostaining was calculated by H-score, and correlations to clinical factors performed using χ 2 or Fisher's exact test. Associations with RFS and OS were assessed using univariate and multivariate Cox proportional hazard models. Survival estimates were generated using the Kaplan-Meier method. RESULTS: In three distinct datasets spanning 684 samples, RANK mRNA expression was higher in primary tumors derived from TNBC patients than from those with other molecular subtypes (P < 0.01). Cell surface-localized RANK protein was consistently higher in TNBC cell lines (P = 0.037). In clinical samples, TNBC patients that expressed both RANK and RANKL proteins had significantly worse RFS (P = 0.0032) and OS (P = 0.004) than patients with RANK-positive, RANKL-negative tumors. RANKL was an independent, poor prognostic factor for RFS (P = 0.04) and OS (P = 0.01) in multivariate analysis in samples that expressed both RANK and RANKL. CONCLUSIONS: RANK and RANKL co-expression is associated with poor RFS and OS in patients with TNBC.

Osteoporosis Risk Calculators.

Osteoporosis is a silent disease until fractures occur, patient recognition is the greatest clinical challenge. Although more than 20 million women in the US are estimated to have established osteoporosis the majority are not appropriately identified. Bone densitometry is the current gold standard for diagnosis of osteoporosis; but may not be feasible or cost-effective to recommend for all postmenopausal women. Therefore, questionnaires incorporating risk factors have been developed to aid the clinician in identifying women with osteoporosis. We will review Qfracture, CAnadian Risk for Osteoporosis Calculator (CAROC), the Simple Calculated Osteoporosis Risk Index (SCORE), the Osteoporosis Risk Assessment Index (ORAI), the Osteoporotic Self-assessment Tool (OST), ABONE, and the United States Preventive Services Task Force recommendations.

Pediatric nephrogenic systemic fibrosis is rarely reported: a RADAR report.

BACKGROUND: Nephrogenic systemic fibrosis is a fibrosing disorder associated with exposure to gadolinium-based contrast agents in people with severely compromised renal function. OBJECTIVE: The purpose of this study was to determine the reported number of cases of nephrogenic systemic fibrosis in children using three distinct publicly available data sources. MATERIALS AND METHODS: We conducted systematic searches of the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS), the International Center for Nephrogenic Systemic Fibrosis Research (ICNSFR) registry and published literature from January 1997 through September 2012. We contacted authors of individual published cases to obtain follow-up data. Data sets were cross-referenced to eliminate duplicate reporting. RESULTS: We identified 23 children with nephrogenic systemic fibrosis. Seventeen had documented exposure to gadolinium-based contrast agents. Six children had been reported in both the FAERS and the literature, four in the FAERS and the ICNSFR registry and five in all three data sources. CONCLUSION: Nephrogenic systemic fibrosis has been rarely reported in children. Although rules related to confidentiality limit the ability to reconcile reports, active pharmaco-vigilance using RADAR (Research on Adverse Drug events And Reports) methodology helped in establishing the number of individual pediatric cases within the three major data sources.

Endocrinology of menopause.

Menopause is a natural process that occurs in women's lives as part of normal aging. Many women go through the menopausal transition with few or no symptoms, while some have significant, or even disabling, symptoms. This manuscript reviews the physiologic processes and symptoms connected with menopause and the diseases associated with menopause, as well as how menopausal symptoms are managed.

Malnutrition and overall survival in older patients with cancer.

BACKGROUND & AIMS: In this study, we assessed the prevalence of malnutrition and its association with overall survival among patients with cancer aged 65 years and older. METHODS: In this retrospective cohort study, patients receiving cancer care underwent a comprehensive geriatric assessment (CGA). Malnutrition status was determined through the CGA. We used univariate and multivariable Cox regression survival analyses to assess the association between baseline malnutrition and survival. RESULTS: A total of 454 patients with cancers were included in the analysis. The median age was 78 years and men and women were equally represented. Forty-two percent (n = 190) were malnourished at baseline, and 33% died during the follow-up (range 0.2-51.1 month). Univariate analysis showed that malnutrition increased the risk of all-cause mortality in older patients with cancer (HR, 1.49; 95% CI, 1.08-2.05; p = 0.01). In the multivariate Cox regression model, malnutrition increased the risk of all-cause mortality (HR, 1.87; 95% CI, 1.10-3.17; p = 0.02) in older patients with solid tumors. However, malnutrition did not increase the risk of all-cause mortality for hematologic malignancies. CONCLUSIONS: In our study, we found that malnutrition was a risk factor for mortality in older cancer patients, especially in older patients with solid tumors. Prospective inter ventional studies are recommended.

Quality of reporting of serious adverse drug events to an institutional review board: a case study with the novel cancer agent, imatinib mesylate.

PURPOSE: Serious adverse drug event (sADE) reporting to Institutional Review Boards (IRB) is essential to ensure pharmaceutical safety. However, the quality of these reports has not been studied. Safety reports are especially important for cancer drugs that receive accelerated Food and Drug Administration approval, like imatinib, as preapproval experience with these drugs is limited. We evaluated the quality, accuracy, and completeness of sADE reports submitted to an IRB. EXPERIMENTAL DESIGN: sADE reports submitted to an IRB from 14 clinical trials with imatinib were reviewed. Structured case report forms, containing detailed clinical data fields and a validated causality assessment instrument, were developed. Two forms were generated for each ADE, the first populated with data abstracted from the IRB reports, and the second populated with data from the corresponding clinical record. Completeness and causality assessments were evaluated for each of the two sources, and then compared. Accuracy (concordance between sources) was also assessed. RESULTS: Of 115 sADEs reported for 177 cancer patients to the IRB, overall completeness of adverse event descriptions was 2.4-fold greater for structured case report forms populated with information from the clinical record versus the corresponding forms from IRB reports (95.0% versus 40.3%, P < 0.05). Information supporting causality assessments was recorded 3.5-fold more often in primary data sources versus IRB adverse event descriptions (93% versus 26%, P < 0.05). Some key clinical information was discrepant between the two sources. CONCLUSIONS: The use of structured syndrome-specific case report forms could enhance the quality of reporting to IRBs, thereby improving the safety of pharmaceuticals administered to cancer patients.

The validity of three malnutrition screening markers among older patients with cancer.

BACKGROUND: Malnutrition is common in older adults with cancer and is associated with adverse clinical outcomes. We assessed and compared the validity of three tools commonly used to screen for malnutrition: The Mini Nutritional Assessment (MNA), weight loss and body mass index (BMI). METHODS: In this retrospective study, we reviewed patients over age 65 with a diagnosis of cancer who were treated at the MD Anderson Cancer Center between 1 January 2013 and 31 March 2017. All patients in this study were evaluated by a trained geriatrician as part of a comprehensive geriatric assessment (CGA). Malnutrition was diagnosed by both CGA and clinical examination. The sensitivity, specificity and Cohen's κ of each tool was also compared with the clinical diagnosis. RESULTS: A total of 454 older patients with cancer who had malnutrition information available were included in the analyses. The median age was 78%, and 42% (n=190) were clinically diagnosed with malnutrition at baseline. When the MNA was performed, 105 out of 352 patients (30%) were malnourished, and 122 (35%) at risk of malnutrition. Weight loss >3 kg was seen in 183 out of 359 (51%) patients, and BMI <20 kg/m2 was found in 30 of the 454 (7%) patients. MNA had the highest validity (area under curve (AUC)=0.83) and reliability (κ=0.67), weight loss had moderate validity (AUC=0.73) and reliability (κ=0.46), while BMI had the lowest validity (AUC=0.55) and reliability (κ=0.55). CONCLUSIONS: For clinical practice, MNA should be incorporated for standard assessment/screening for these older patients with cancer.

Overall survival in older patients with cancer.

OBJECTIVES: A growing number of patients with cancer are older adults. We sought to identify the predictors for overall survival (OS) in older adults with solid tumour and haematological malignancies between January 2013 and December 2016. METHODS: Retrospective cohort study. A comprehensive geriatric assessment was performed, with a median follow-up of 12.8 months. ANALYSIS: univariate and multivariate Cox proportional hazards regression analysis. RESULTS: In this study, among the 455 patients with last follow-up date or date of death, 152 (33.4%) died during the follow-up. The median follow-up is 12.8 months (range 0.2-51.1 months) and the median OS is 20.5 months (range 0.3-44.5 months). Among all older patients with cancer, predictors of OS included male gender, cancer stage, malnutrition, history of smoking, heavy alcohol use, frailty, weight loss, major depression, low body weight and nursing home residence. Traditional performance scores (Eastern Cooperative Oncology Group (ECOG) and Karnofsky Performance Scale (KPS)) were predictors of OS. Independent predictors included age >85 years and haematological malignancies. Among solid tumours (n=311) in addition to the above predictors, comorbidity, gait speed and vitamin D deficiency were associated with OS. CONCLUSIONS: We identified specific geriatric factors associated with OS in older patients with cancer, and comparable in predictive ability to traditional performance scores such as KPS and ECOG. Prospective studies will be necessary to confirm our findings.

Osteoporosis-related Vertebral Fragility Fractures: A Review and Analysis of the American Orthopaedic Association's Own the Bone Database.

STUDY DESIGN: Retrospective cohort study of the Own the Bone database which is a fracture liaison service designed to improve recognition and treatment of osteoporosis. OBJECTIVE: To use the Own the Bone (OTB) database to 1) examine the specific demographics of patients presenting with a low-energy clinical vertebral fracture (VFX) and 2) compare demographic and fracture-specific risk factors between patients with clinical VFX versus patients with nonvertebral low-energy fracture (NVFX). SUMMARY OF BACKGROUND DATA: Large database studies have described risk factors for developing VFX. It is well described that a history of previous VFX portends an increased risk of future VFX. Few studies have reported cohorts from a fracture liaison service such as the OTB initiative. METHODS: 35,039 unique cases of fragility fracture occurred between 2009 and 2016 and were included in analysis. VFX accounted for 3395 (9.9%) of the presenting fractures at OTB enrollment. The demographics, lifestyle factors, medication use, and fracture-specific data for patients in the OTB registry with vertebral fractures were summarized and then statistically compared to those with nonvertebral fragility fractures. RESULTS: The majority of VFX patients were Caucasian, postmenopausal women (74.4%). There was an increased likelihood of presenting with a vertebral fracture in patients who sustained a previous VFX after the age of 50, while patients who sustained a prior nonvertebral fracture (NVFX) were more likely to present with a subsequent NVFX. After controlling for patients with a history of fracture after the age of 50, VFX patients (vs. NVFX) were more likely to be age 70-79, class 1 obesity, with a history of taking anti-osteoporotic prescription medications. CONCLUSIONS: Multiple factors were associated with a significantly increased risk of VFX compared with NVFX. Understanding the risk factors unique to fragility VFX is a critical component for targeting "at-risk" patients and preventing future osteoporosis-related fractures and their consequences. LEVEL OF EVIDENCE: 4.

Pharmacovigilance and reporting oversight in US FDA fast-track process: bisphosphonates and osteonecrosis of the jaw.

More than half of all serious adverse reactions are identified 7 or more years after a drug receives approval from the US Food and Drug Administration (FDA). In 2002, 9 months after the intravenous bisphosphonate zoledronic acid received regulatory approval for marketing, the FDA received reports of nine patients with cancer, who were treated with zoledronic acid, who unexpectedly developed osteonecrosis of the jaw. During the next 2 years, three oral surgeons described 104 patients with cancer with osteonecrosis of the jaw in the medical literature and identified intravenous bisphosphonate therapy as being common to the care of these patients. In subspecialty medical, radiology, and dental journals, case reports and case series described clinical features of osteonecrosis of the jaw in patients with cancer who were treated with bisphosphonates. Manufacturer-sponsored epidemiological studies reported the first estimates of the incidence of this toxic effect, ranging from 0.1% to 1.8%. By contrast, independent epidemiological efforts from clinicians and the International Myeloma Foundation reported incidence estimates between 5% and 10%. Between 2003 and 2005, warnings about the risks of bisphosphonate-associated osteonecrosis were disseminated by national regulatory agencies, the manufacturers of bisphosphonates, and the International Myeloma Foundation. From 2006, independent clinical recommendations for diagnosis, prevention, and treatment of this toxic effect have been disseminated by manufacturers, national regulatory authorities, the International Myeloma Foundation, and medical specialty organisations. Furthermore, independent efforts by pharmaceutical manufacturers, dental and medical professionals, a non-profit organisation (the International Myeloma Foundation), patients, and regulatory authorities has led to the rapid identification and dissemination of safety information for this serious adverse reaction. Better coordination of safety-related pharmacovigilance initiatives is now needed.

Malnutrition and overall survival in older adults with cancer: A systematic review and meta-analysis.

BACKGROUND: Some studies have shown that malnutrition is associated with increased risk of mortality in older adults with cancer. However, evidence of its effect is limited and inconsistent. To assess the effect of malnutrition on overall survival in older adults with cancer, we performed a meta-analysis of available studies. METHODS: We systematically searched MEDLINE, EMBASE, Web of Science, CINAHL, and PsycINFO for observational studies that examined the association between malnutrition and risk of mortality in older adults with cancer (≥65 years). Malnutrition is defined according to assessment and screening tools in different studies. Older adults with malnutrition were compared with those with normal nutrition for overall survival. A random-effect model was fitted to estimate the summary relative risk (RR) and 95% confidence interval (CI). Between-studies heterogeneity was measured with the I2 statistic. RESULTS: Ten studies met the inclusion criteria, and a total of 4692 older adults with cancer were included in the meta-analysis. Heterogeneity existed among the different studies (I2 = 73.7%, p < 0.01). Malnutrition was significantly positively associated with increased risk of all-cause mortality (RR: 1.73; 95% CI: 1.23-2.41) compared with those with good nutrition status. A sensitivity analysis of 2773 older adults with cancer on the malnutrition assessed by Mini Nutrition Assessment (MNA), found that malnutrition is still associated with higher risk for all-cause mortality (RR = 2.13, 95% CI: 1.34-3.39). CONCLUSION: Our meta-analysis of observational studies found a significant effect of malnutrition on overall survival in older adults with cancer.

Prevalence and factors associated with malnutrition in older patients with cancer.

BACKGROUND: >60% of patients with cancer are 65 years of age and older, and malnutrition is commonly encountered in older adults. OBJECTIVE: To assess the prevalence and factors associated with malnutrition in older patients with cancer. METHODS: In this cross-sectional study, patients with cancer underwent a comprehensive geriatric assessment (CGA). Malnutrition status was diagnosed by clinical assessment including screening tools such as Mini Nutrition Assessment (MNA), weight loss, and BMI. ANALYSIS: Descriptive statistics, chi-Square and logistic regression analysis were used to assess factors associated with malnutrition. RESULTS: A total of 454 patients with malnutrition information available were included in analysis. The median age was 78, range 65-96 years and comorbid diagnoses included dementia, mild cognitive impairment, frailty, and functional impairment. A total of 41.9% (n = 190) were diagnosed with malnutrition during the CGA. In the multivariable analysis, major depression and frailty were significantly associated with malnutrition. After controlling for potential confounders, patients who had malnutrition were 2.53-times more likely to have major depression (OR = 2.53, 95% CI: 1.23-5.24, p = 0.01) and 3.82 times more likely to have frailty (OR = 3.82, 95% CI: 1.35-10.84, p = 0.01) than those without malnutrition. CONCLUSIONS: Despite significant advances in cancer and supportive care, malnutrition remains a significant and highly prevalent public health problem among older patients with cancer. Identifying factors associated with risk for malnutrition in this patient population can help develop preventive strategies as part of care. Prospective studies are recommended.

Management of Osteoporosis in Survivors of Adult Cancers With Nonmetastatic Disease: ASCO Clinical Practice Guideline.

PURPOSE: The aim of this work is to provide evidence-based guidance on the management of osteoporosis in survivors of adult cancer. METHODS: ASCO convened a multidisciplinary Expert Panel to develop guideline recommendations based on a systematic review of the literature. RESULTS: The literature search of the 2018 systematic review by the US Preventive Services Task Force in the noncancer population was used as the evidentiary base upon which the Expert Panel based many of its recommendations. A total of 61 additional studies on topics and populations not covered in the US Preventive Services Task Force review were also included. Patients with cancer with metastatic disease and cancer survival outcomes related to bone-modifying agents are not included in this guideline. RECOMMENDATIONS: Patients with nonmetastatic cancer may be at risk for osteoporotic fractures due to baseline risks or due to the added risks that are associated with their cancer therapy. Clinicians are advised to assess fracture risk using established tools. For those patients with substantial risk of osteoporotic fracture, the clinician should obtain a bone mineral density test. The bone health of all patients may benefit from optimizing nutrition, exercise, and lifestyle. When a pharmacologic agent is indicated, bisphosphonates or denosumab at osteoporosis-indicated dosages are the preferred interventions.

Evaluation of serious adverse drug reactions: a proactive pharmacovigilance program (RADAR) vs safety activities conducted by the Food and Drug Administration and pharmaceutical manufacturers.

BACKGROUND: The Food and Drug Administration (FDA) and pharmaceutical manufacturers conduct most postmarketing pharmaceutical safety investigations. These efforts are frequently based on data mining of databases. In 1998, investigators initiated the Research on Adverse Drug events And Reports (RADAR) project to investigate reports of serious adverse drug reactions (ADRs) and prospectively obtain information on these cases. We compare safety efforts for evaluating serious ADRs conducted by the FDA and pharmaceutical manufacturers vs the RADAR project. METHODS: We evaluated the completeness of serious ADR descriptions in the FDA and RADAR databases and the comprehensiveness of notifications disseminated by pharmaceutical manufacturers and the RADAR investigators. A serious ADR was defined as an event that led to death or required intensive therapies to reverse. RESULTS: The RADAR investigators evaluated 16 serious ADRs. Compared with descriptions of these ADRs in FDA databases (2296 reports), reports in RADAR databases (472 reports) had a 2-fold higher rate of including information on history and physical examination (92% vs 45%; P<.001) and a 9-fold higher rate of including basic science findings (34% vs 4%; P = .08). Safety notifications were disseminated earlier by pharmaceutical suppliers (2 vs 4 years after approval, respectively), although notifications were less likely to include information on incidence (46% vs 93%; P = .02), outcomes (8% vs 100%; P<.001), treatment or prophylaxis (25% vs 93%; P<.001), or references (8% vs 80%; P<.001). CONCLUSION: Proactive safety efforts conducted by the RADAR investigators are more comprehensive than those conducted by the FDA and pharmaceutical manufacturers, but dissemination of related safety notifications is less timely.

Osteoporosis and its implications for dental patients.

BACKGROUND: Osteoporosis is a common disease in middle-aged and older Americans. The risk of sustaining fractures is a concern, and mortality rates after hip or vertebral fractures are high. Oral health maintenance for adults with osteoporosis is important. TYPES OF STUDIES REVIEWED: The authors conducted a MEDLINE search of the medical and dental literature with the objective of reviewing osteoporosis, its effect on public health in the population in the United States and the implications in providing dental care for these patients. They selected studies by performing a content search with National Library of Medicine medical subject headings (epidemiology, public health impact, treatment, adverse drug reactions, cost-effectiveness of osteoporosis therapy, oral health, periodontal disease, adverse drug reactions, bisphosphonates and osteonecrosis of the jaw). They then performed a study design search with a filter so that only randomized clinical trials were included. RESULTS: Osteoporosis and related fractures are more common than coronary disease, stroke and breast cancer. Fractures resulting from osteoporosis can affect a patient's quality of life severely, and fractures result in functional impairment and increased health care cost and mortality. Medical management of osteoporosis includes diet control, with appropriate intake of calcium and vitamin D, weight-bearing exercise, discontinuation of tobacco and alcohol intake, and use of medications, including selective estrogen receptor modulators, calcitonin, anabolic agents and bisphosphonates. Bisphosphonates have been associated with the development of osteonecrosis of the jaws. CLINICAL IMPLICATIONS: Oral health maintenance is important in patients with osteoporosis. Bisphosphonate therapy or other medical treatment for these people should be discontinued only after consultation with the patient's physician.

Updated recommendations for managing the care of patients receiving oral bisphosphonate therapy: an advisory statement from the American Dental Association Council on Scientific Affairs.

BACKGROUND: and Overview. In 2005, the American Dental Association (ADA) Council on Scientific Affairs convened an expert panel to develop clinical recommendations for dentists treating patients who are receiving oral bisphosphonate therapy. The Journal of the American Dental Association published the resulting report in 2006. This 2008 advisory statement is the first of projected periodic updates of the 2006 clinical recommendations. CONCLUSION: This 2008 advisory statement concludes, on the basis of a review of the current literature, that for patients receiving bisphosphonate therapy, the risk of developing bisphosphonate-associated osteonecrosis (BON) of the jaw apparently remains low. It also newly concludes that current screening and diagnostic tests are unreliable for predicting a patient's risk of developing the condition. This statement updates the 2006 recommendations regarding general dentistry, management of periodontal diseases, implant placement and maintenance, oral and maxillofacial surgery, endodontics, restorative dentistry and prosthodontics, and orthodontics.

Venous thromboembolism and mortality associated with recombinant erythropoietin and darbepoetin administration for the treatment of cancer-associated anemia.

CONTEXT: The erythropoiesis-stimulating agents (ESAs) erythropoietin and darbepoetin are licensed to treat chemotherapy-associated anemia in patients with nonmyeloid malignancies. Although systematic overviews of trials have identified venous thromboembolism (VTE) risks, none have identified mortality risks with ESAs. OBJECTIVE: To evaluate VTE and mortality rates associated with ESA administration for the treatment of anemia among patients with cancer. DATA SOURCES: A published overview from the Cochrane Collaboration (search dates: January 1, 1985-April 1, 2005) and MEDLINE and EMBASE databases (key words: clinical trial, erythropoietin, darbepoetin, and oncology), the public Web site of the US Food and Drug Administration and ESA manufacturers, and safety advisories (search dates: April 1, 2005-January 17, 2008). STUDY SELECTION: Phase 3 trials comparing ESAs with placebo or standard of care for the treatment of anemia among patients with cancer. DATA EXTRACTION: Mortality rates, VTE rates, and 95% confidence intervals (CIs) were extracted by 3 reviewers from 51 clinical trials with 13 611 patients that included survival information and 38 clinical trials with 8172 patients that included information on VTE. DATA SYNTHESIS: Patients with cancer who received ESAs had increased VTE risks (334 VTE events among 4610 patients treated with ESA vs 173 VTE events among 3562 control patients; 7.5% vs 4.9%; relative risk, 1.57; 95% CI, 1.31-1.87) and increased mortality risks (hazard ratio, 1.10; 95% CI, 1.01-1.20). CONCLUSIONS: Erythropoiesis-stimulating agent administration to patients with cancer is associated with increased risks of VTE and mortality. Our findings, in conjunction with basic science studies on erythropoietin and erythropoietin receptors in solid cancers, raise concern about the safety of ESA administration to patients with cancer.