Clinical Trials Logo

Clinical Trial Summary

Osteoporotic fractures are associated with significant morbidity, increased mortality and reduction in the quality of life, available treatments reduces the fracture risk between 30 and 70%, however some patients experience a new fracture and/or continue to loose bone during treatment; this has been defined as treatment failure (TF). The epidemiology and biological bases of TF are currently under-investigated, thus it is impossible for the physician to forecast patients' answer to treatment. The aims of TAILOR study are to collect sounded epidemiological data on TF in a real life setting. To this extent, the investigators will retrospectively a large cohort of 5000 patients with at least 60 months of anti-osteoporotic treatment followed in our center for the diagnosis and care of bone metabolic diseases, and compare TF patients to adequate responders (ARs) for clinical characteristic and biological parameters. The results will be a "signature" to identify those patients who will experience TF.


Clinical Trial Description

Fragility fractures represent a major clinical burden in the increasingly older population. Old suffering with femoral fractures will die within a year (15-25%) or become dependent (50%). Costs associated with fractures have been estimated to be 32 billion EUR/year in Europe, 20 billion USD in the United States and 12.5 billion USD in China. The second fracture worsen the patients' health and increases costs, the financial burden imposed by second fractures on the United States healthcare system has been calculated in 2 billion USD/year. The efficacy of treatment in osteoporosis relies in the reduction of the fracture risk: drugs approved for osteoporosis reduce the risk of fractures between 30-70% for vertebral fractures, 40-50% for hip fractures and 15-20% for non-vertebral fractures (1,2). However, no available treatment reset the fracture risk to zero. Treatment efficacy is assumed by a significant reduction in fracture risk supported by an increase in bone mineral density (BMD) and a decrease in markers of bone turnover. The question if a new fracture or bone loss may be considered a treatment failure is highly debated, recently, a position paper of the International Osteoporosis Foundation described the treatment failure (TF) based on the occurrence of two fractures or one fracture plus lack of variation in BMD, markers of bone turnover or both while on treatment (3). The study of TF and its prevention is crucial, as the correct and precocious identification of the patients that will not benefit from the first line drugs, will prevent unsuccessful treatment and reduce sanitary costs. Several factors has been suggested to be associated with TF, however, until now, the therapeutic decision relies entirely on physician expertise and not on decisional algorithms. The aim of this project is to characterize the clinical characteristics foreseeing TF. The identification of a signature for TF will increase the standard care of osteoporotic patients reducing the burden due to a new fracture. TAILOR will pave the way for the generation of a new algorithm to choose wisely a personalize therapeutical approach for osteoporotic patients, taking into account their clinical characteristics, thus minimizing the risk of TF, improving patients quality and expectancy of life and reducing sanitary costs. 2. Experimental Design and Approach. Retrospective study on patients on treatment with anti-resorptives or anabolics for primary osteoporosis. All the patients evaluated in the out-patients service of the unit between 2009 and 2019 (about 5000 subjects) will evaluated, medical records of patients are available, medical records with missing information will be excluded. The investigators will include in the analyses women affected by post-menopausal osteoporosis treated for at least 12 months and up to 10 years with drugs active on bone turnover and with at least one follow-up visit in the 10-year period considered. TF will be diagnosed according to the position paper of the IOF (3): occurrence of two fragility fractures while on treatment or one fracture plus lack of variation BMD, biochemical markers or both. Fragility fracture will be defined because of a fall from the standing position or a mechanical effort without fall. Spinal fractures have be certified by radiography or DXA morphometry whereas for non-vertebral fractures, a hospital discharge or physician report will be also considered valid evidence of fracture. Fractures of the skull, face, cervical spine, fingers, and toes will not be included in our study. Patients will be considered ARs when they completed 60 months on treatment with no incident fractures according with Diez-Perez et al. (4), for teriparatide the period considered will be 24 months. Patients will be classified according to the type of drug used (SERMs, oral bisphosphonates, iv bisfosfonates, denosumab or teriparatide), for each patients the following information will be recorded: age, post-menopausal period, assumption of calcium and vitamin D, presence and site of fragility fractures, BMD, serum levels of calcium, phosphate, PTH, creatinine, 25OHvitaminD, markers of bone turnover, adverse events. This information will be recorded at the baseline and at each follow-up visit. The decision of the physician expert in osteoporosis management during the follow-up visit will be recorded (i.d. continue the ongoing treatment or change drug, new drugs prescribed). Patients will be classified as TF based on the occurrence of two fractures while on treatment or one fracture plus lack of variation in bone mineral density (BMD), biochemical markers or both(3). Statistical analyses. The power analysis was conducted using an estimated medium effect size (f = 0.25), an alpha level of 0.05, and a power of 0.95 using the software G*power. According to statistical computing, a sample size of n = 400 is required. The percentage of TF within different treatment and will be compared with AR by means of ANCOVA for analyzed variables. the medical decision taken by the physician expert in bone metabolic disorders after treatment failure (the patient will continue the treatment/switch to another treatment/stop treatment) will be analysed. References 1. Body J-J, Bergmann P, Boonen S, Boutsen Y, Devogelaer J-P, Goemaere S, Kaufman J-M, Rozenberg S, Reginster J-Y. Evidence-based guidelines for the pharmacological treatment of postmenopausal osteoporosis: a consensus document by the Belgian Bone Club. Osteoporos Int. 2010 Oct;21(10):1657-80. 2. MacLean C, Newberry S, Maglione M, McMahon M, Ranganath V, Suttorp M, Mojica W, Timmer M, Alexander A, McNamara M, Desai SB, Zhou A, Chen S, Carter J, Tringale C, Valentine D, Johnsen B, Grossman J. Systematic review: comparative effectiveness of treatments to prevent fractures in men and women with low bone density or osteoporosis. Ann Intern Med. 2008 Feb 5;148(3):197-213. 3. Diez-Perez A, Adachi JD, Agnusdei D, Bilezikian JP, Compston JE, Cummings SR, Eastell R, Eriksen EF, Gonzalez-Macias J, Liberman UA, Wahl DA, Seeman E, Kanis JA, Cooper C, IOF CSA Inadequate Responders Working Group. Treatment failure in osteoporosis. Osteoporos Int. 2012 Dec;23(12):2769-74. 4. Díez-Pérez A, González-Macías J. Inadequate responders to osteoporosis treatment: proposal for an operational definition. Osteoporos Int. 2008 Nov;19(11):1511-6. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT05499403
Study type Observational
Source Centre Hospitalier Universitaire Vaudois
Contact
Status Completed
Phase
Start date May 1, 2022
Completion date February 6, 2024

See also
  Status Clinical Trial Phase
Active, not recruiting NCT06287502 - Efficacy of Structured Exercise-Nutritional Intervention on Sarcopenia in Patients With Osteoporosis N/A
Completed NCT03822078 - Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Denosumab (AMG 162) in Japanese Postmenopausal Women Phase 1
Recruiting NCT05845021 - Surgeon-Initiated Bone Health Referral Pathway in Patients Undergoing Lower Extremity Arthroplasty N/A
Completed NCT00092066 - A Study to Evaluate the Safety, Tolerability, and Efficacy of an Investigational Drug and Dietary Supplement in Men and Postmenopausal Women With Osteoporosis (0217A-227) Phase 3
Recruiting NCT04754711 - Interest of Nutritional Care of Children With Sickle Cell Disease on Bone Mineral Density and Body Composition N/A
Completed NCT04736693 - Replication of the HORIZON Pivotal Fracture Trial in Healthcare Claims Data
Not yet recruiting NCT06431867 - Primary Care Management of Osteoporosis in Older Women
Completed NCT02922478 - Role of Comorbidities in Chronic Heart Failure Study
Recruiting NCT02616627 - Association Between DXA Results and the Complications, Clinical Courses and Outcomes in Chronic Dialysis Patients
Recruiting NCT02635022 - Fragility Fracture Liaison Service and Anti-osteoporosis Medication Monitoring Service Study
Active, not recruiting NCT02617303 - Prevention of Falls and Its Consequences in Elderly People N/A
Completed NCT02566655 - Clinical Trial of Intravenous Infusion of Fucosylated Bone Marrow Mesenchyme Cells in Patients With Osteoporosis Phase 1
Completed NCT03420716 - Symbiotic Yogurt, Calcium Absorption and Bone Health in Young Adult Women N/A
Completed NCT02559648 - Denosumab vs Placebo in Patients With Thalassemia Major and Osteoporosis Phase 2
Not yet recruiting NCT02223572 - Secondary Fracture Prevention in Patients Who Suffered From Osteoporotic Fracture N/A
Completed NCT02003716 - DeFRA Questionnaire as an Anamnestic Form N/A
Not yet recruiting NCT01854086 - Compliance and Persistence With Osteoporosis Treatment and Attitude Towards Future Therapy Among Post-menopausal Israeli Women During Drug Treatment or Drug Holiday N/A
Unknown status NCT01913834 - Nasally and sc Administered Teriparatide in Healthy Volunteers Phase 1
Completed NCT01757340 - Calorie Restriction With Leucine Supplementation N/A
Completed NCT01694784 - Understanding and Discouraging Overuse of Potentially Harmful Screening Tests N/A