RESUMEN
Current guidelines recommend primary osteoporosis screening for at-risk men to reduce the morbidity, mortality, and cost associated with osteoporotic fractures. However, analyses in a national Veterans Health Administration cohort of over 4,000,000 men demonstrated that primary osteoporosis screening as it is currently operationalized does not benefit most older Veterans due to inefficient targeting and low subsequent treatment and adherence rates. The overall objective of this study is to determine whether a new model of primary osteoporosis screening reduces fracture risk compared to usual care. We are conducting a pragmatic group randomized trial of 38 primary care teams assigned to usual care or a Bone Health Service (BHS) screening model in which screening and adherence activities are managed by a centralized expert team. The study will: 1) compare the impact of the BHS model on patient-level outcomes strongly associated with fracture rates (eligible proportion screened, proportion meeting treatment criteria who receive osteoporosis medications, medication adherence, and femoral neck bone mineral density); 2) quantify the impact on provider and facility-level outcomes including change in DXA volume, change in metabolic bone disease clinic volume, and PACT provider time and satisfaction; and 3) estimate the impact on health system and policy outcomes using Markov models of screening program cost per quality adjusted life year based from health system and societal perspectives.
Asunto(s)
Osteoporosis , Fracturas Osteoporóticas , Densidad Ósea , Humanos , Masculino , Tamizaje Masivo/métodos , Morfolinas , Osteoporosis/diagnóstico por imagen , Osteoporosis/epidemiología , Fracturas Osteoporóticas/epidemiología , Fracturas Osteoporóticas/prevención & control , Años de Vida Ajustados por Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
In contrast to recommendations for young and middle-aged adults, intentional weight loss among older adults remains controversial and is inconsistently advised. Recent research suggests that a higher protein diet can mitigate loss of lean mass during periods of intentional weight loss among older adults with obesity; however, the effects of intentional weight loss on skeletal muscle and bone are not fully understood. The Dairy in the Diet Yields New Approaches for Muscle Optimization (DDYNAMO) trial is a 6-month, randomized, controlled pilot study assessing the effects of combining regular, generous intakes of high quality protein (30 g/meal; primarily from dairy) with caloric restriction (-500kcal/d) and low-intensity resistance exercise (30 min/3 times per week) on muscle quality, muscle composition, bone mineral density in men and women aged ≥60 years with obesity and mild to moderate functional impairment (Short Physical Performance Battery [SPPB] score ≥4 to ≤10). Participants will be re-assessed at 18 months to evaluate weight maintenance, bone mineral density, physical function, and other secondary measures. ClinicalTrials.gov Identifier: NCT02437643.
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Densidad Ósea/fisiología , Dieta Reductora/métodos , Proteínas en la Dieta/metabolismo , Músculo Esquelético/fisiología , Obesidad , Pérdida de Peso/fisiología , Anciano , Índice de Masa Corporal , Restricción Calórica/métodos , Femenino , Estado Funcional , Humanos , Masculino , Obesidad/diagnóstico , Obesidad/dietoterapia , Obesidad/metabolismo , Obesidad/fisiopatología , Evaluación de Resultado en la Atención de Salud , Proyectos Piloto , Entrenamiento de Fuerza/métodosRESUMEN
The Trial of Parkinson's And Zoledronic acid (TOPAZ, https://clinicaltrials.gov/ct2/show/NCT03924414 ) is a unique collaboration between experts in movement disorders and osteoporosis to test the efficacy of zoledronic acid, an FDA-approved parenteral treatment for osteoporosis, for fracture prevention in people with neurodegenerative parkinsonism. Aiming to enroll 3,500 participants age 65 years or older, TOPAZ is one of the largest randomized, placebo-controlled clinical trials ever attempted in parkinsonism. The feasibility of TOPAZ is enhanced by its design as a U.S.- wide home-based trial without geographical limits. Participants receive information from multiple sources, including specialty practices, support groups and websites. Conducting TOPAZ in participants' homes takes advantage of online consent technology, the capacity to confirm diagnosis using telemedicine and the availability of research nursing to provide screening and parenteral therapy in homes. Home-based clinical research may provide an efficient, convenient, less expensive method that opens participation in clinical trials to almost anyone with parkinsonism.
RESUMEN
Bisphosphonates are first line agents used to treat osteoporosis and reduce fracture rate. They bind to areas of exposed calcium in the skeleton and cause osteoclast apoptosis, thereby leading to a reduction in remodelling rates. They are also used to decrease skeletal complications of some cancers including a reduction in bone metastases. Following the landmark randomised controlled trial of zoledronate post hip fracture (HORIZON) in which an unexpected survival benefit was found, there has been increasing interest in their potential ability to increase lifespan. This review will consider the clinical evidence for their effect on mortality in both the osteoporosis and non-osteoporosis settings, the latter including studies in intensive care, cancer and cardiovascular disease. Where evidence exists, this review will briefly discuss some of the postulated mechanisms for this survival benefit.
Asunto(s)
Conservadores de la Densidad Ósea , Osteoporosis , Conservadores de la Densidad Ósea/uso terapéutico , Difosfonatos/uso terapéutico , Humanos , Longevidad , Osteoporosis/tratamiento farmacológico , Ácido Zoledrónico/uso terapéuticoRESUMEN
Zoledronate is the most potent and most long-acting bisphosphonate in clinical use, and is administered as an intravenous infusion. Its major uses are in osteoporosis, Paget's disease, and in myeloma and cancers to reduce adverse skeletal related events (SREs). In benign disease, it is a first- or second-line treatment for osteoporosis, achieving anti-fracture efficacy comparable to that of the RANKL blocker, denosumab, over 3 years, and it reduces fracture risk in osteopenic older women. It is the preferred treatment for Paget's disease, achieving higher rates of remissions which are much more prolonged than with any other agent. Some trials have suggested that it reduces mortality, cardiovascular disease and cancer, but these findings are not consistent across all studies. It is nephrotoxic, so should not be given to those with significant renal impairment, and, like other potent anti-resorptive agents, can cause hypocalcemia in patients with severe vitamin D deficiency, which should be corrected before administration. Its most common adverse effect is the acute phase response, seen in 30-40% of patients after their first dose, and much less commonly subsequently. Clinical trials in osteoporosis have not demonstrated increases in osteonecrosis of the jaw or in atypical femoral fractures. Observational databases are currently inadequate to determine whether these problems are increased in zoledronate users. Now available as a generic, zoledronate is a cost-effective agent for fracture prevention and for management of Paget's disease, but wider provision of infusion facilities is important to increase patient access. There is a need to further explore its potential for reducing cancer, cardiovascular disease and mortality, since these effects could be substantially more important than its skeletal actions.
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Conservadores de la Densidad Ósea , Osteítis Deformante , Osteoporosis , Anciano , Conservadores de la Densidad Ósea/efectos adversos , Difosfonatos/efectos adversos , Femenino , Humanos , Osteítis Deformante/tratamiento farmacológico , Ácido Zoledrónico/uso terapéuticoRESUMEN
Acetylcholinesterase inhibitors (AChEIs) have been noted to increase bone density and quality in mice. Human studies are limited but suggest an association with improved bone healing after hip fracture. We examined the relationship between AChEI use and fracture risk in a national cohort of 360,015 male veterans aged 65 to 99 years with dementia but without prior fracture using Veterans Affairs (VA) hospital, Medicare, and pharmacy records from 2000 to 2010. Diagnosis of dementia, any clinical fracture (excluding facial and digital), comorbidities, and medications were identified using ICD-9 and drug class codes. Cox proportional hazard models considering AChEI use as a time-varying covariate and adjusting for fall and fracture risk factors compared the time-to-fracture in AChEI users versus non-AChEI users. Potential confounders included demographics (age, race, body mass index), comorbidities associated with fracture or falls (diabetes, lung disease, stroke, Parkinson's, seizures, etc.) and medications associated with fracture or falls (bisphosphonates, glucocorticoids, androgen deprivation therapy [ADT], proton pump inhibitors [PPIs], selective serotonin receptor inhibitors [SSRIs], etc.). Competing mortality risk was considered using the methods of Fine and Gray. To account for persistent effects on bone density or quality that might confer protection after stopping the medication, we completed a secondary analysis using the medication possession ratio (MPR) as a continuous variable in logistic regression models and also compared MPR increments of 10% to minimal/no use (MPR 0 to <0.10). Among older veterans with diagnosis of dementia, 20.1% suffered a fracture over an average of 4.6 years of follow-up. Overall, 42.3% of the cohort were prescribed AChEIs during the study period. The hazard of any fracture among AChEI users compared with those on other/no dementia medications was significantly lower in fully adjusted models (hazard ratio [HR] = 0.81; 95% confidence interval [CI] 0.75-0.88). After considering competing mortality risk, fracture risk remained 18% lower in veterans using AChEIs (HR = 0.82; 95% CI 0.76-0.89). © 2019 American Society for Bone and Mineral Research. Published 2019. This article is a U.S. Government work and is in the public domain in the USA.
Asunto(s)
Demencia , Fracturas de Cadera , Neoplasias de la Próstata , Veteranos , Anciano , Antagonistas de Andrógenos , Animales , Inhibidores de la Colinesterasa , Humanos , Masculino , Medicare , Ratones , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
Diabetes mellitus among older men has been associated with increased bone mineral density but paradoxically increased fracture risk. Given the interactions among medication treatment, glycemic control, and diabetes-associated comorbidities, the relative effects of each factor remains unclear. This retrospective study includes 652,901 male veterans aged ≥65 years with diabetes and baseline hemoglobin A1c (HbA1c) value. All subjects received primary care in the Veterans Health Administration (VHA) from 2000 to 2010. Administrative data included ICD9 diagnoses and pharmacy records and was linked to Medicare fee-for-service data. Hazard ratios (HR) for any clinical fracture and hip fracture were calculated using competing risk hazards models, adjusted for fracture risk factors including age, race/ethnicity, body mass index (BMI), alcohol and tobacco use, rheumatoid arthritis, corticosteroid use, as well as diabetes-related comorbidities including cardiovascular disease, chronic kidney disease, and peripheral neuropathy. HbA1c <6.5% was associated with a higher risk of any clinical fracture (HR = 1.08, 95% confidence interval [CI] 1.06-1.11) compared with the reference HbA1c of 7.5% to 8.5%. Fracture risk was not increased among those with A1c ≥8.5%, nor among those with A1c 6.5% to 7.5%. Use of insulin was independently associated with greater risk of fracture (HR = 1.10, 95% CI 1.07-1.12). There was a significant interaction between insulin use and HbA1c level, (p < 0.001), such that those using insulin with HbA1c <6.5% had HR = 1.23 and those with HbA1c 6.5% to 7.5% had HR = 1.15. Metformin use was associated with decreased fracture risk (HR = 0.88, 95% CI 0.87-0.90). We conclude that among older men with diabetes, those with HbA1c lower than 6.5% are at increased risk for any clinical and hip fracture. Insulin use is associated with higher fracture risk, especially among those with tight glycemic control. Our findings demonstrate the importance of the treatment regimen and avoiding hypoglycemia for fracture prevention in older men with diabetes. © 2019 American Society for Bone and Mineral Research.
Asunto(s)
Complicaciones de la Diabetes , Diabetes Mellitus Tipo 2 , Fracturas Óseas , Hipoglucemia , Insulina/administración & dosificación , Metformina/administración & dosificación , Anciano , Anciano de 80 o más Años , Densidad Ósea , Complicaciones de la Diabetes/sangre , Complicaciones de la Diabetes/prevención & control , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Fracturas Óseas/sangre , Fracturas Óseas/prevención & control , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemia/sangre , Hipoglucemia/prevención & control , Masculino , Estudios Retrospectivos , Factores de Riesgo , Estados Unidos , United States Department of Veterans AffairsRESUMEN
OBJECTIVE: To determine the association between dual-energy x-ray absorptiometry (DXA) testing for osteoporosis and subsequent fractures in US male veterans without a previous fracture. PATIENTS AND METHODS: This is a propensity score-matched observational study using Centers for Medicare and Medicaid Services and Veterans Affairs (VA) data from January 1, 2000, through December 31, 2010, with a mean follow-up time of 4.7 years (range, 0-10 years). Men receiving VA primary care aged 65 to 99 years without a previous fracture (N=2,539,812) were included. Men undergoing DXA testing were propensity score matched with untested controls in a 1:3 ratio, indicating the probability of DXA testing within the next year. Time to first clinical fracture was the primary outcome. Comorbidities, demographic characteristics, medications, DXA results, and osteoporosis treatment were defined using administrative data and natural language processing. A landmark analysis contingent on surviving to 12 months after screening was completed, accounting for competing risk of mortality. RESULTS: During follow-up of 153,311 men tested by DXA and 390,158 controls, 56,083 (10.3%) had sustained a fracture and 111,774 (20.6%) died. Overall, DXA testing was not associated with a decrease in fractures; conclusions are limited by unmeasured confounders and low medication initiation and adherence in those meeting treatment thresholds (12% of follow-up time). In contrast, DXA testing in prespecified subgroups was associated with a lower risk of fracture in comparison to the overall population who underwent DXA testing: androgen deprivation therapy (hazard ratio [HR], 0.77; 95% CI, 0.66-0.89), glucocorticoids (HR, 0.77; 95% CI, 0.72-0.84), age 80 years and older (HR, 0.85; 0.81-0.90), 1 or more VA guideline risk factors (HR, 0.91; 95% CI, 0.87-0.95), and high Fracture Risk Assessment Tool using body mass index score (HR, 0.90; 95% CI, 0.86-0.95). CONCLUSION: Current VA DXA testing practices are ineffective overall; interventions to improve treatment adherence are needed. Targeted DXA testing in higher-risk men was associated with a lower fracture risk.
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Fracturas Óseas/epidemiología , Tamizaje Masivo/estadística & datos numéricos , Osteoporosis/diagnóstico por imagen , Absorciometría de Fotón/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Comorbilidad , Estudios de Seguimiento , Humanos , Masculino , Modelos de Riesgos Proporcionales , Factores de Riesgo , Factores Sexuales , Estados Unidos/epidemiología , United States Department of Veterans Affairs , Veteranos/estadística & datos numéricosRESUMEN
Introduction: Type 2 diabetes mellitus among older women has been associated with increased bone mineral density, but paradoxically with increased fracture risk. Findings among older men have varied, and potential mechanisms have not been fully elucidated. Methods: A retrospective study of male veterans 65 to 99 years of age who received primary care in the Veterans Health Administration from 2000 to 2010, using administrative data from all 146 Veterans Health Administration medical centers linked to Centers for Medicare and Medicaid Services Medicare fee-for-service data. Potential mediating factors of the diabetes-associated risk were evaluated using negative binomial regression models with the outcomes of any clinical fracture and hip fracture. Results: Of 2,798,309 Veterans included in the cohort, 900,402 (32.3%) had a diagnosis of diabetes. After adjusting for age, race, ethnicity, body mass index, alcohol and tobacco use, rheumatoid arthritis, and corticosteroid use, the risk of any clinical fracture associated with diabetes was 1.22 (95% confidence interval, 1.21 to 1.23) and that of hip fracture was 1.21 (95% confidence interval, 1.19 to 1.23). Significant mediating factors included peripheral neuropathy, cardiovascular disease, and congestive heart failure, with 45.5% of the diabetes-associated fracture risk explained by these diagnoses. Conclusions: Older male Veterans with diabetes have a 22% increased risk of incident clinical fracture compared with those without. A significant portion of this risk is explained by diabetes-related comorbidities, specifically peripheral neuropathy and congestive heart failure. Identification of these mediating factors suggests possible mechanisms, as well as potential interventions.
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Enfermedades Cardiovasculares/etiología , Complicaciones de la Diabetes/etiología , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/etiología , Fracturas de Cadera/etiología , Anciano , Anciano de 80 o más Años , Densidad Ósea , Enfermedades Cardiovasculares/patología , Comorbilidad , Complicaciones de la Diabetes/patología , Diabetes Mellitus Tipo 2/fisiopatología , Nefropatías Diabéticas/patología , Estudios de Seguimiento , Fracturas de Cadera/patología , Humanos , Masculino , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Estados Unidos , VeteranosRESUMEN
INTRODUCTON: Low-trauma, osteoporotic fractures among older men are associated with a significant increase in morbidity and mortality. Despite effective therapies for osteoporosis, several studies have demonstrated that management and treatment after a low trauma fracture remains inadequate, especially among men. Fracture liaison services have been shown to significantly improve osteoporosis evaluation and treatment. However, such programs may be less feasible and accessible in rural areas, with limited availability of specialty services. The study objective was to evaluate a centralized, electronic consult (e-consult) program serving multiple veterans administration medical centers, including the geographic scope, accessibility to rural patients, and impact on osteoporosis evaluation and treatment. METHODS: The e-consult program identified veterans with potential osteoporotic fractures from inpatient and outpatient encounter data, based on ICD9 diagnosis codes (800-829) from the central data warehouse. The medical record of an eligible patient was reviewed by a bone health specialist, and an e-consult note was sent to the patient's primary care provider that specified guideline-based recommendations for further evaluation and management. A bone health nurse liaison then coordinated the ordering and follow-up of laboratory and bone density assessment, osteoporosis education (eg medication administration and side effects, calcium and vitamin D supplementation, falls prevention, and exercise), and adherence follow-up via telephone. Patients were identified as living in a rural area if their ZIP code was not in a US Census Bureau-defined urban area (ie population density greater than approximately 386 persons per square kilometer/1000 persons per square mile). RESULTS: From October 2013 to September 2014, 2775 fractures were identified by a fracture-related ICD9 code. After exclusion of those aged less than 50 years and high-trauma fractures, 321 e-consults were completed. Of those, 171 (53.3%) were for patients residing in a rural or highly rural area. The e-consult program saved a total of 19 187 km (11 917 miles) of travel. For rural patients, bisphosphonates were recommended 51 times, with 33 (64.7%) ordered, and bone density assessments were recommended 109 times with 79 (72.5%) ordered. A nurse liaison significantly improved bisphosphonate ordering (from 39.7% to 75.8%) and bone mineral density testing completion rates (from 37.1% to 63.0%), for both rural and urban patients (p<0.01). CONCLUSIONS: A centralized e-consult program can effectively and efficiently provide specialty bone health services to patients residing in rural areas. The program was able to save substantial travel time and increase the rates of evaluation and treatment for osteoporosis.
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Tamizaje Masivo/estadística & datos numéricos , Fracturas Osteoporóticas/epidemiología , Derivación y Consulta/estadística & datos numéricos , Consulta Remota/estadística & datos numéricos , Población Rural/estadística & datos numéricos , Registros Electrónicos de Salud/estadística & datos numéricos , Femenino , Humanos , Masculino , Fracturas Osteoporóticas/rehabilitación , Evaluación de Resultado en la Atención de Salud , Pautas de la Práctica en MedicinaRESUMEN
PURPOSE: With ethical requirements to the enrollment of lower risk subjects, osteoporosis trials are underpowered to detect reduction in hip fractures. Different skeletal sites have different levels of fracture risk and response to treatment. We sought to identify fracture sites which cluster with hip fracture at higher than expected frequency; if these sites respond to treatment similarly, then a composite fracture endpoint could provide a better estimate of hip fracture reduction. METHODS: Cohort study using Veterans Affairs and Medicare administrative data. Male Veterans (n=5,036,536) aged 50-99 years receiving VA primary care between 1999 and 2009 were included. Fractures were ascertained using ICD9 and CPT codes and classified by skeletal site. Pearson correlation coefficients, logistic regression and kappa statistics were used to describe the correlation between each fracture type and hip fracture within individuals, without regard to the timing of the events. RESULTS: 595,579 (11.8%) men suffered 1 or more fractures and 179,597 (3.6%) suffered 2 or more fractures during the time under study. Of those with one or more fractures, the rib was the most common site (29%), followed by spine (22%), hip (21%) and femur (20%). The fracture types most highly correlated with hip fracture were pelvic/acetabular (Pearson correlation coefficient 0.25, p<0.0001), femur (0.15, p<0.0001), and shoulder (0.11, p<0.0001). CONCLUSIONS: Pelvic, acetabular, femur, and shoulder fractures cluster with hip fractures within individuals at greater than expected frequency. If we observe similar treatment risk reductions within that cluster, subsequent trials could consider the use of a composite endpoint to better estimate hip fracture risk.
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Fémur/lesiones , Fracturas de Cadera/epidemiología , Húmero/lesiones , Fracturas Osteoporóticas/epidemiología , Pelvis/lesiones , Anciano , Anciano de 80 o más Años , Conservadores de la Densidad Ósea , Ensayos Clínicos como Asunto , Estudios de Cohortes , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Osteoporosis/complicaciones , Selección de PacienteRESUMEN
OBJECTIVES: Few studies have assessed the effectiveness of different drugs for osteoporosis (OP). We aimed to determine if fracture and mortality rates vary among patients initiating different OP medications. METHODS: We used the Medicare 5% sample to identify new users of intravenous (IV) zoledronic acid (n=1.674), oral bisphosphonates (n=32.626), IV ibandronate (n=492), calcitonin (n=2.606), raloxifene (n=1.950), or parathyroid hormone (n=549). We included beneficiaries who were ≥65 years of age, were continuously enrolled in fee-for-service Medicare and initiated therapy during 2007-2009. Outcomes were hip fracture, clinical vertebral fracture, and all-cause mortality, identified using inpatient and physician diagnosis codes for fracture, procedure codes for fracture repair, and vital status information. Cox regression models compared users of each medication to users of IV zoledronic acid, adjusting for multiple confounders. RESULTS: During follow-up (median, 0.8-1.5 years depending on the drug), 787 subjects had hip fractures, 986 had clinical vertebral fractures, and 2.999 died. Positive associations included IV ibandronate with hip fracture (adjusted hazard ratio (HR), 2.37; 95% confidence interval (CI) 1.25-4.51), calcitonin with vertebral fracture (HR=1.59, 95%CI 1.04-2.43), and calcitonin with mortality (HR=1.31; 95%CI 1.02-1.68). Adjusted HRs for other drug-outcome comparisons were not statistically significant. CONCLUSIONS: IV ibandronate and calcitonin were associated with higher rates of some types of fracture when compared to IV zolendronic acid. The relatively high mortality associated with use of calcitonin may reflect the poorer health of users of this agent.
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Conservadores de la Densidad Ósea/uso terapéutico , Fracturas de Cadera/mortalidad , Fracturas de Cadera/prevención & control , Osteoporosis/tratamiento farmacológico , Osteoporosis/mortalidad , Fracturas Osteoporóticas/mortalidad , Fracturas Osteoporóticas/prevención & control , Fracturas de la Columna Vertebral/prevención & control , Anciano , Anciano de 80 o más Años , Conservadores de la Densidad Ósea/administración & dosificación , Causas de Muerte , Bases de Datos Factuales , Femenino , Fracturas de Cadera/diagnóstico , Humanos , Masculino , Medicare , Osteoporosis/diagnóstico , Fracturas Osteoporóticas/diagnóstico , Factores de Riesgo , Fracturas de la Columna Vertebral/diagnóstico , Fracturas de la Columna Vertebral/mortalidad , Factores de Tiempo , Resultado del Tratamiento , Estados UnidosRESUMEN
OBJECTIVE: The aim of this guideline was to formulate practice guidelines for the diagnosis and treatment of Paget's disease of the bone. PARTICIPANTS: The guideline was developed by an Endocrine Society-appointed Task Force of experts, a methodologist, and a medical writer. EVIDENCE: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. CONSENSUS PROCESS: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of The Endocrine Society and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines. Two systematic reviews were conducted to summarize supporting evidence. CONCLUSIONS: We recommend that plain radiographs be obtained of the pertinent regions of the skeleton in patients with suspected Paget's disease. If the diagnosis is confirmed, we suggest that a radionucleotide bone scan be done to determine the extent of the disease. After diagnosis of Paget's disease, we recommend measurement of serum total alkaline phosphatase or, when warranted, a more specific marker of bone formation or bone resorption to assess the response to treatment or evolution of the disease in untreated patients. We suggest treatment with a bisphosphonate for most patients with active Paget's disease who are at risk for future complications. We suggest a single 5-mg dose of iv zoledronate as the treatment of choice in patients who have no contraindication. In patients with monostotic disease who have a normal serum total alkaline phosphatase, we suggest that a specific marker of bone formation and bone resorption be measured, although these may still be normal. Serial radionuclide bone scans may determine the response to treatment if the markers are normal. We suggest that bisphosphonate treatment may be effective in preventing or slowing the progress of hearing loss and osteoarthritis in joints adjacent to Paget's disease and may reverse paraplegia associated with spinal Paget's disease. We suggest treatment with a bisphosphonate before surgery on pagetic bone.