Prospective Evaluation of Biomarkers Variability in Knee Prosthetic Surgery

NCT ID: NCT01971931

Last Updated: 2020-01-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

40 participants

Study Classification

OBSERVATIONAL

Study Start Date

2013-06-30

Study Completion Date

2017-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Knee Osteoarthritis

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

PROSPECTIVE

Study Groups

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Patients undergoing TKR.

No interventions assigned to this group

Eligibility Criteria

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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
Minimum Eligible Age

40 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Milan

OTHER

Sponsor Role lead

Responsible Party

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Pietro Randelli, MD

Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Emanuela Galliera, PhD

Role: PRINCIPAL_INVESTIGATOR

Istituto Ortopedico Galeazzi IRCCS, Milano, Italy

Randelli Pietro, MD

Role: STUDY_DIRECTOR

Policlinico San Donato IRCCS, San Donato Milanese, Italy

Corsi Romanelli M. Massimiliano, MD

Role: PRINCIPAL_INVESTIGATOR

Policlinico San Donato IRCCS, San Donato Milanese, Italy

Locations

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Policlinico San Donato (Istituto di Ricovero e Cura a Carattere Scientifico)

San Donato Milanese, Milano, Italy

Site Status

Countries

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Italy

References

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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.

Reference Type BACKGROUND
PMID: 17895323 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20623281 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16105967 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7744919 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15156331 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11021450 (View on PubMed)

Mertens MT, Singh JA. Biomarkers in arthroplasty: a systematic review. Open Orthop J. 2011 Mar 16;5:92-105. doi: 10.2174/1874325001105010092.

Reference Type BACKGROUND
PMID: 21584201 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21187538 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23140091 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11409560 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20513875 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23154036 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30072203 (View on PubMed)

Other Identifiers

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BioBone01

Identifier Type: -

Identifier Source: org_study_id

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