Knee Osteoarthritis
Conditions
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.
Interventions
None listed
Sponsors
University of Milan
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in knee function score after surgery | 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. |
| Change in knee pain scale after surgery | One day before surgery; 3, 6, 12 months after surgery | For evaluation of knee pain, patients will be asked to indicate their knee pain on a visual analogue scale (VAS). |
Countries
Italy
Outcome results
None listed