Prospective Evaluation of Biomarkers Variability in Knee Prosthetic Surgery

Completed

• Conditions: Knee Osteoarthritis

• Registration Number: NCT01971931
• Lead Sponsor: University of Milan

Brief 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.

The primary goal of this study is to measure serum and tissue levels of some proteins involved in bone remodelling.

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.

Study Timeline

• Study Start: 2013-06
• Study First Submitted: 2013-07-05
• Study First Submitted QC: 2013-10-23
• Study First Posted: 2013-10-30
• Primary Completion: 2016-12
• Study Completion: 2017-12
• Status Verified: 2020-01
• Last Update Submitted: 2020-01-21
• Last Update Posted: 2020-01-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Change in biomarkers serum level after surgery	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.

Secondary Outcome Measures

Name	Time	Method
Change in periprosthetic bone density after surgery	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.
Biomarkers mRNA expression	Baseline	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.

Trial Locations

Locations (1)

Policlinico San Donato (Istituto di Ricovero e Cura a Carattere Scientifico); 🇮🇹 San Donato Milanese, Milano, Italy