S 03/10 CFP Hip Prosthesis

S 03/10 "Bone Metabolic Response to CFP Hip Prosthesis with and without Denosumab. A randomized Clinical F-PET/CT and DXA Study."
Dr. Gösta Ullmark MD. PhD., Centre for Research & Development, Uppsala University, Ortoped Kliniken, Gävle

Abstracts 1-4:

1. Temporal changes in [18F]PET/CT and biomarkers in patients with unilateral osteoarthritis of the hip, OAH, operated with the uncemented CFP®-stem. Six months of Follow-up.
A. Nyström1, D Kiritopoulos1, S Lazarinis1, G Ullmark2, J Sörensen3, J Milbrink1, N Hailer1, H Mallmin1.
1Ort. Klin. Akademiska sjukhuset, 2Ort Klin Gävle Lasarett, 3PET-Centrum, Akademiska sjukhuset
Introduction: Uncemented total hip arthroplasty (THA) is associated with periprosthetic loss of bone mineral density, BMD.
Patients and Methods: We investigated the relation between periprosthetic Standardized Uptake Value, SUV(osteoblastic activity), by [18F]PET/CT; biochemical markers for bone metabolism, i.e. morning fasting blood samples for a bone formation marker, P1NP and a bone resorption marker, Crosslaps and BMD, by DXA. Fifteen patients (age 60±4, 11 females), controls in a RCT, were operated with a CFP®-stem (hydroxiapatite coated titanium stem), Waldemar Link, and were followed for six months. Changes from baseline were analysed using Wilcoxon signed rank test. Statistical significant changes p<0.05 were considered relevant.

Results: SUV in “Gruen” 1-7 increased by 76% at 3 months and 54% at 6 months. Preoperatively P1NP was 46(±17), decreased immediately after surgery to 31(±14) and increased at 3 (80±38) and 6 months (56±24). S-βCrossLaps decreased immediately after surgery from 480(±209) ng/l to 383(±183)ng/l. At 3 and 6 months there was no change from baseline. BMD in Gruen zone 7 decreased by 16% at 6 months.
Discussion: A previous study has shown that periprosthetic BMD for the CFP®-stem decreases already at 3 months. This study confirms this but also shows that bone formation measured as SUV and P1NP, increases during the first six months after THA.
Conclusion: Bone formation increases during the first 6 months postop but there is a net loss of BMD in Gruen zone 7.

2. Subgroup analysis of a Randomised Clinical Trial, RCT: Effects of Denosumab in patients with unilateral osteoarthritis of the hip, OAH, operated with an uncemented CFP®-stem. Six months of follow-up.
A. Nyström1, D Kiritopoulos1, S Lazarinis1, G Ullmark2, J Sörensen3, J Milbrink1, N Hailer1, H Mallmin1.
1Ort. Klin. Akademiska sjukhuset, 2Ort Klin Gävle Lasaret, 3PetCentrum, Akademiska sjukhuset
Introduction. Uncemented total hip arthroplasty (THA) is associated with loss of bone mineral density, BMD, at the proximal part of the femur after two years.
Patients and Methods: We conducted an RCT to investigate if the antiresorptive effect of Denosumab can prevent periprosthetic bone loss.
Thirty one patients (age 59±5) patients were randomised to two subcutaneous injections with 1 ml Denosumab, or 1 ml NaCl starting within the first two days after surgery and after six months. The patients were investigated for Standardised Uptake Value, SUV(osteoblastic activity), by [18F]PET/CT, biochemical markers for bone metabolism, i.e. morning fasting blood samples for a bone formation marker, P1NP, and a bone resorption marker, Crosslaps and BMD by DXA.
Linear models were used to evaluate treatment differences with respect to, SUV, biochemical markers of bone turnover and BMD.
Results:
The Denosumab group showed a 26% increase in SUV at six months, compared to 76% in the placebo group. (p=0.02).
The Denosumab group showed a 12% reduction in P1NP level, compared to 23% increase in the placebo group. (p<0.05).
The Denosumab group showed a 54% reduction in Crosslap level, compared to a 10% reduction in the placebo group. (p=0.0006).
The Denosumab group showed a 5% reduction in BMD in Gruen zone 7, compared to 18% reduction in the placebo group (p=0.06)
Discussion: The increase in SUV, in zones corresponding to Gruen 1-7, was much smaller in the Denosumab group. This indicates that bone turnover of periprosthetic bone is reduced by Denosumab which is in accordance with the changes in biomarkers.
Conclusion: Denosumab reduces periprosthetic bone turnover.

3. Temporal changes in [18F]PET/CT and biomarkers in patients with unilateral osteoarthritis of the hip, OAH, operated with the uncemented Continuum®-cup. Six months of Follow-up.
D Kiritopoulos1, A. Nyström1, S Lazarinis1, G Ullmark2, J Sörensen3, J Milbrink1, N Hailer1, H Mallmin1.
1Ort. Klin. Akademiska sjukhuset, 2Ort Klin Gävle Lasarett, 3PetCentrum, Akademiska sjukhuset
Introduction. Uncemented total hip arthroplasty (THA) is associated with periprosthetic loss of bone mineral density, BMD.
Patients and Methods. We investigated the relation between periprosthetic (Digas zones) Standardized Uptake Value, SUV(osteoblastic activity), by [18F]PET/CT, BMD, by DXA, and biochemical markers for bone metabolism, i.e. morning fasting blood samples for a bone formation marker, P1NP and a bone resorption marker, Crosslaps. Sixteen patients, (age 60+4, 4 males, 12 females) controls in a RCT, were operated with an uncemented Continuum®cup, Zimmer Co(pressfit, trabecular metal surface) and were followed for six months. Changes were analysed using Wilcoxon signed rank test. Statistical significant changes p<0.05 were considered relevant.
Results:. A decrease was demonstrated in SUV Digas zone 1 (4.7+1.5, p< 0.05,) and Digas zones 1-5 (18+6, p=0.0002,). An increase was observed in bone formation marker P1NP (, 58+24, p=0.008) but not in bone resorption marker Crosslaps. No significant change were found in periprosthetic BMD (Digas zone 1 and sum of Digas zones 1-5) at six months after surgery
Discussion: The trauma of the surgery seems to increase P1NP as proven in previous studies and to decrease the periprosthetic osteoblast response at the Continuumcup. However, no statistically significant changes in periprosthetic BMD were found.
Conclusion: We conclude that there is a decrease in SUV around the Continuum® cup, six months after surgery with an uncemented THA, in contrast to an increase in the bone formation marker P1NP.

4. Subcohort analysis of a Randomised Clinical Trial, RCT: Effects of Denosumab in patients with unilateral osteoarthritis of the hip, OAH, operated with an uncemented Continuum-cup®. Six months of follow-up.
D Kiritopoulos1, A. Nyström1, S Lazarinis1, G Ullmark2, J Sörensen3, J Milbrink1, N Hailer1, H Mallmin1.
1Ort. Klin. Akademiska sjukhuset, 2Ort Klin. Gävle Lasarett, 3PetCentrum, Akademiska sjukhuset
Introduction. Uncemented total hip arthroplasty (THA) is associated with loss of bone mineral density, BMD, around the proximal part of the cup after two years.
Patients and Methods: We conducted a RCT to investigate whether a human monoclonal antibody(IgG2), Denosumab, can prevent periprosthetic bone loss in patients with unilateral OAH, operated with an uncemented Continuum-cup®.
Thirty-two patients (age 59+5, 13 males, 19 females) were randomised into two subcutaneous injections of Denosumab or placebo, directly after surgery and after six months. They were investigated for Standard Uptake Value, SUV, by [18F]PET/CT, BMD, by DXA and biochemical markers for bone metabolism, i.e. morning fasting blood samples for a bone formation marker, P1NP, and a bone resorption marker, Crosslaps.
Linear models were used to explain changes in SUV, P1NP, Crosslaps and BMD compared to baseline.
Results:
In zone 1 and sum of zones 1-5, the Denosumab group developed a bigger reduction in SUV, than the placebo group, but the difference was not statistically significant.
P1NP level decreased in the Denosumab group, while the placebo group had an increase (p=0.04). Crosslaps level decreased more in Denosumab group than in the placebo group (p=0.0005).
In Digas zone 1, the Denosumab group increased in BMD while the placebo group decreased (p=0.04). In Digas zones 1-5 the Denosumab group increased in BMD, while the placebo group remained at the baseline level (p=0.03).
Conclusion: Denosumab reduces periprosthetic bone turnover, also verified by the biomarkers, and prevents BMD loss around the Continuum-cup® in the short-term.