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Knee OsteoarthritisNCT01971931

Prospective Evaluation of Biomarkers Variability in Knee Prosthetic Surgery

An observational study of Knee Osteoarthritis, run by University of Milan at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 40 to 80 years
Conditions the study is for
Knee Osteoarthritis
How many people
40 participants
Where
1 siteItaly
Study dates
Jun 2013to Dec 2017
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: Patients undergoing TKR surgery.

Who may be able to join

  • Age > 40, <80
  • Indication for TKR
  • Surgical indication for PFC Sigma®, posterior stabilized, mobile bearing TKR
  • Patients signed written informed consent

Who cannot join

  • 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
Show all 11Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Italy1 site

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

    San Donato Milanese, Milano, 20097

Other trials in Italy

About this study

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.

Read the detailed description

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.

Medical subject headings
Osteoarthritis, Knee

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT01971931
Study groupRoleWhat they receive
Patients undergoing TKR.Not described

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in biomarkers serum level 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.

    Measured: One day before surgery; 3 months after surgery and 12 months after surgery

Secondary outcomes (2)

  1. Change in periprosthetic bone density 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.

    Measured: 3, 6, 12 months after surgery

  2. Biomarkers mRNA expression

    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.

    Measured: Baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Oct 2013 (estimated)
  2. Study startJun 2013
  3. Primary completionDec 2016
  4. Study completionDec 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Case only
Time perspective
Prospective
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01971931
Sponsor's protocol ID
BioBone01
Status last verified
Jan 2020
First submitted
5 Jul 2013
Last updated
22 Jan 2020
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • 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.

    PubMed 17895323

  • 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.

    PubMed 20623281

  • 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.

    PubMed 16105967

  • 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.

    PubMed 7744919

  • 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.

    PubMed 15156331

  • 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.

    PubMed 11021450

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

    PubMed 21584201

  • 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.

    PubMed 21187538

  • 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.

    PubMed 23140091

  • 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.

    PubMed 11409560

  • 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.

    PubMed 20513875

  • 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.

    PubMed 23154036

  • 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.

    PubMed 30072203

Questions about this trial

What is this clinical trial studying?

An observational study of Knee Osteoarthritis, run by University of Milan at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in biomarkers serum level after surgery (time frame: One day before surgery; 3 months after surgery and 12 months after surgery). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01971931, which also lists 13 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2020.

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