- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT01971931
Prospective Evaluation of Biomarkers Variability in Knee Prosthetic Surgery
Bone quality is an important factor influencing the outcome of total knee replacement (TKR) surgery. Therefore, assessing bone quality preoperatively could help the surgeon in the choice of the most appropriate prosthetic implant.
The primary goal of this study is to measure serum and tissue levels of some proteins involved in bone remodelling.
Aperçu de l'étude
Statut
Les conditions
Description détaillée
Aseptic implant loosening after TKR causes knee pain, reduces knee function and may require revision surgery.
Several proteins have been identified, which are involved in bone metabolism and remodelling; variations in serum levels of some of these proteins after TKR loosening have also been described.
However, preoperative identification of risk factors for aseptic loosening remains a challenge.
An observational study is conducted to evaluate how levels of the following serum biomarkers vary after TKR:
- osteoprotegerin (OPG)
- receptor activator of nuclear factor kappa-B (RANK)
- receptor activator of nuclear factor kappa-B ligand (RANK-L)
- sclerostin
- cathepsin K
To avoid bias caused by inflammatory states, C reactive protein (CRP), interleukin 1 (IL-1), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) levels and erythrocyte sedimentation rate (ESR) will be measured.
Secondary goals are to evaluate the mRNA expression of OPG, RANK-L, cathepsin K and sclerostin on tibial bone biopsies and to study if changes in serum biomarkers levels after surgery are associated with:
- clinical outcomes
- periprosthetic bone density
- variation of two bone reabsorption markers, the postoperative change of which has already been described in details: type 1 collagen cross-linked C-terminal telopeptide (CTP1) and type 1 procollagen N-terminal telopeptide (P1NP).
One day before surgery, after having signed informed consent, patients will undergo a vertebral and femoral dual-energy X-ray absorptiometry (DEXA) scan and blood samples will be collected.
During surgery a tibial biopsy will be collected. Between 4 and 7 days postoperatively and 3, 6 and 12 months after surgery patients will again undergo periprosthetic DEXA scans and blood samples will be collected.
Type d'étude
Inscription (Réel)
Contacts et emplacements
Lieux d'étude
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Milano
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San Donato Milanese, Milano, Italie, 20097
- Policlinico San Donato (istituto di ricovero e cura a carattere scientifico)
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
Méthode d'échantillonnage
Population étudiée
La description
Inclusion Criteria:
- Age > 40, <80
- Indication for TKR
- Surgical indication for PFC Sigma®, posterior stabilized, mobile bearing TKR
- Patients signed written informed consent
Exclusion Criteria:
- Age > 80, < 40
- TKR revision surgery
- Fixed knee deformities greater than 15° in varus, valgus, flexion or tibial slope.
- Knee ankylosis
- Paget's disease
- Hyperparathyroidism
- Patient treated with: bisphosphonates, strontium ranelate, selective estrogen receptor modulators for osteoporosis, calcitonin, denosumab.
- Informed consent not accepted
- Serious comorbidity
- Active infections
- Pregnant or breastfeeding women
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
Cohortes et interventions
Groupe / Cohorte |
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Patients undergoing TKR.
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Change in biomarkers serum level after surgery
Délai: One day before surgery; 3 months after surgery and 12 months after surgery
|
OPG, RANK, RANK-L, sclerostin, cathepsin K, CTP1 and P1NP levels will be assessed on blood samples.
CRP, IL-1, IL-6, TNF-α and ESR will also be measured to identify inflammatory states.
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One day before surgery; 3 months after surgery and 12 months after surgery
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Change in periprosthetic bone density after surgery
Délai: 3, 6, 12 months after surgery
|
Variations of tibial bone density will be evaluated repeating DEXA scans 3, 6 and 12 months after surgery.
A preoperative vertebral and femoral DEXA scan will be used to estimate patient's initial bone density.
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3, 6, 12 months after surgery
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Biomarkers mRNA expression
Délai: Baseline
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OPG, RANK-L , cathepsin K, sclerostin and CTP1 mRNA levels will be estimated using Real-Time polymerase chain reaction (RT-PCR) on tibial plateau biopsies.
RT-PCR will be performed simultaneously on all samples, after collection of all biopsies.
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Baseline
|
Autres mesures de résultats
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Change in knee function score after surgery
Délai: One day before surgery; 3, 6, 12 months after surgery
|
For evaluation of knee function, patients will be asked to fill in the Oxford Knee Score (OKS) questionnaire.
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One day before surgery; 3, 6, 12 months after surgery
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Change in knee pain scale after surgery
Délai: One day before surgery; 3, 6, 12 months after surgery
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For evaluation of knee pain, patients will be asked to indicate their knee pain on a visual analogue scale (VAS).
|
One day before surgery; 3, 6, 12 months after surgery
|
Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: Emanuela Galliera, PhD, Istituto Ortopedico Galeazzi IRCCS, Milano, Italy
- Directeur d'études: Randelli Pietro, MD, Policlinico San Donato IRCCS, San Donato Milanese, Italy
- Chercheur principal: Corsi Romanelli M. Massimiliano, MD, Policlinico San Donato IRCCS, San Donato Milanese, Italy
Publications et liens utiles
Publications générales
- Ryd L, Albrektsson BE, Carlsson L, Dansgard F, Herberts P, Lindstrand A, Regner L, Toksvig-Larsen S. Roentgen stereophotogrammetric analysis as a predictor of mechanical loosening of knee prostheses. J Bone Joint Surg Br. 1995 May;77(3):377-83.
- Minoda Y, Ikebuchi M, Kobayashi A, Iwaki H, Inori F, Nakamura H. A cemented mobile-bearing total knee replacement prevents periprosthetic loss of bone mineral density around the femoral component: a matched cohort study. J Bone Joint Surg Br. 2010 Jun;92(6):794-8. doi: 10.1302/0301-620X.92B6.23159.
- Pijls BG, Valstar ER, Nouta KA, Plevier JW, Fiocco M, Middeldorp S, Nelissen RG. Early migration of tibial components is associated with late revision: a systematic review and meta-analysis of 21,000 knee arthroplasties. Acta Orthop. 2012 Dec;83(6):614-24. doi: 10.3109/17453674.2012.747052. Epub 2012 Nov 9.
- Vega D, Maalouf NM, Sakhaee K. CLINICAL Review #: the role of receptor activator of nuclear factor-kappaB (RANK)/RANK ligand/osteoprotegerin: clinical implications. J Clin Endocrinol Metab. 2007 Dec;92(12):4514-21. doi: 10.1210/jc.2007-0646. Epub 2007 Sep 25.
- Colombini A, Lombardi G, Galliera E, Dogliotti G, Randelli P, Meerssemann A, Mineo G, Cabitza P, Corsi MM. Plasma and drainage fluid levels of soluble receptor activator of nuclear factor-kB (sRANK), soluble receptor activator of nuclear factor-kB ligand (sRANKL) and osteoprotegerin (OPG) during proximal humerus fracture healing. Int Orthop. 2011 May;35(5):777-82. doi: 10.1007/s00264-010-1088-3. Epub 2010 Jul 11.
- Rogers A, Eastell R. Circulating osteoprotegerin and receptor activator for nuclear factor kappaB ligand: clinical utility in metabolic bone disease assessment. J Clin Endocrinol Metab. 2005 Nov;90(11):6323-31. doi: 10.1210/jc.2005-0794. Epub 2005 Aug 16.
- Li MG, Thorsen K, Nilsson KG. Increased bone turnover as reflected by biochemical markers in patients with potentially unstable fixation of the tibial component. Arch Orthop Trauma Surg. 2004 Jul;124(6):404-9. doi: 10.1007/s00402-004-0695-0. Epub 2004 May 20.
- Li MG, Nilsson KG. The effect of the preoperative bone quality on the fixation of the tibial component in total knee arthroplasty. J Arthroplasty. 2000 Sep;15(6):744-53. doi: 10.1054/arth.2000.6617.
- Mertens MT, Singh JA. Biomarkers in arthroplasty: a systematic review. Open Orthop J. 2011 Mar 16;5:92-105. doi: 10.2174/1874325001105010092.
- Kenanidis EI, Potoupnis ME, Papavasillioul KA, Sayegh FE, Petsatodis GE, Kapetanos GA. Serum levels of bone turnover markers following total joint arthroplasty. J Orthop Surg (Hong Kong). 2010 Dec;18(3):290-5. doi: 10.1177/230949901001800307.
- van Loon CJ, Oyen WJ, de Waal Malefijt MC, Verdonschot N. Distal femoral bone mineral density after total knee arthroplasty: a comparison with general bone mineral density. Arch Orthop Trauma Surg. 2001 May;121(5):282-5. doi: 10.1007/s004020000232.
- Soininvaara TA, Harju KA, Miettinen HJ, Kroger HP. Periprosthetic bone mineral density changes after unicondylar knee arthroplasty. Knee. 2013 Mar;20(2):120-7. doi: 10.1016/j.knee.2012.10.004. Epub 2012 Nov 13.
- Cucchi D, Menon A, Galliera E, Messina C, Zanini B, Marazzi MG, Massaccesi L, Compagnoni R, Corsi Romanelli MM, Randelli P. A Prospective Assessment of Periprosthetic Bone Mineral Density and Osteoimmunological Biomarkers Variations After Total Knee Replacement Surgery. J Clin Densitom. 2019 Jan-Mar;22(1):86-95. doi: 10.1016/j.jocd.2018.05.039. Epub 2018 May 26. Erratum In: J Clin Densitom. 2019 Aug 13;:
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- BioBone01
Plan pour les données individuelles des participants (IPD)
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