Metabolic Response of Human Osteoarthritic Cartilage to Biochemically Characterized Collagen Hydrolysates.

The most frequent disease of the locomotor system is osteoarthritis (OA), which, as a chronic joint disease, might benefit more from nutrition than acute illnesses. Collagen hydrolysates (CHs) are peptidic mixtures that are often used as nutraceuticals for OA. Three CHs were characterized biochemically and pharmacologically. Our biophysical (MALDI-TOF-MS, NMR, AFM) and fluorescence assays revealed marked differences between CHs of fish (Peptan® F 5000, Peptan® F 2000) and porcine (Mobiforte®) origin with respect to the total number of peptides and common peptides between them. Using a novel dual radiolabeling procedure, no CH modulated collagen biosynthesis in human knee cartilage explants. Peptan® F 2000 enhanced the activities of the aggrecanase ADMATS4 and ADMATS5 in vitro without loss of proteoglycan from cartilage explants; the opposite effect was observed with Mobiforte®. Interleukin (IL)-6, matrix metalloproteinase (MMP)-1, -3 and -13 levels were elevated in explants that were treated with Mobiforte® and Peptan® F 5000, but not with Peptan® F 2000. In conclusion, the heterogeneous peptide composition and disparate pharmacological effects between CHs suggest that the effect of a CH preparation cannot be extrapolated to other formulations. Thus, the declaration of a CH as a safe and effective nutraceutical requires a thorough examination of its pleiotropic effects.

Collagen metabolism of human osteoarthritic articular cartilage as modulated by bovine collagen hydrolysates.

Destruction of articular cartilage is a characteristic feature of osteoarthritis (OA). Collagen hydrolysates are mixtures of collagen peptides and have gained huge public attention as nutriceuticals used for prophylaxis of OA. Here, we evaluated for the first time whether different bovine collagen hydrolysate preparations indeed modulate the metabolism of collagen and proteoglycans from human OA cartilage explants and determined the chemical composition of oligopeptides representing collagen fragments. Using biophysical techniques, like MALDI-TOF-MS, AFM, and NMR, the molecular weight distribution and aggregation behavior of collagen hydrolysates from bovine origin (CH-Alpha®, Peptan™ B 5000, Peptan™ B 2000) were determined. To investigate the metabolism of human femoral OA cartilage, explants were obtained during knee replacement surgery. Collagen synthesis of explants as modulated by 0-10 mg/ml collagen hydrolysates was determined using a novel dual radiolabeling procedure. Proteoglycans, NO, PGE(2), MMP-1, -3, -13, TIMP-1, collagen type II, and cell viability were determined in explant cultures. Groups of data were analyzed using ANOVA and the Friedman test (n = 5-12). The significance was set to p≤0.05. We found that collagen hydrolysates obtained from different sources varied with respect to the width of molecular weight distribution, average molecular weight, and aggregation behavior. None of the collagen hydrolysates tested stimulated the biosynthesis of collagen. Peptan™ B 5000 elevated NO and PGE(2) levels significantly but had no effect on collagen or proteoglycan loss. All collagen hydrolysates tested proved not to be cytotoxic. Together, our data demonstrate for the first time that various collagen hydrolysates differ with respect to their chemical composition of collagen fragments as well as by their pharmacological efficacy on human chondrocytes. Our study underscores the importance that each collagen hydrolysate preparation should first demonstrate its pharmacological potential both in vitro and in vivo before being used for both regenerative medicine and prophylaxis of OA.

Follow up of complete subtalar release for clubfoot--Evolution of different scores.

BACKGROUND: Even today there are still some cases of clubfoot that require a more extensive form of treatment. Thus, it is still essential to ascertain the development of the clubfoot after extensive release operations. METHOD: 70 children presenting 99 cases of primary clubfoot (age 8 months-10 years) were followed up after 4.5 and 9 years following complete subtalar release. Function, clinical and radiological results as well as 3 scores were assessed at both dates. RESULTS: Function and pain worsened between the two follow-up periods, whereas objective clinical and radiological results remained equivalent. 44-79% were rated good or excellent depending on the scoring system applied.Older children with primary clubfoot had comparable results to children operated on at a younger age; also pre-operated feet achieved similar results. CONCLUSION: In our opinion the results justify keeping complete release in mind as an alternative method in cases of severe residual and recurrent clubfoot.

Minimal-invasive posterior approach for total hip arthroplasty versus standard lateral approach.

In this prospective study we compared clinical and radiological results and rehabilitation progress of 64 patients who underwent total hip arthroplasty using the standard lateral approach with 64 patients operated with a minimal-invasive (MIS) posterior approach. The outcome of our study did not show any significant differences with regard to patient's safety such as complication rate and radiological assessment of the cup position. There was no difference in the duration of surgery, blood loss, hospital stay and postoperative leg length discrepancy. Rehabilitation milestones were achieved earlier by MIS patients and three and six months postoperatively, the Harris Hip Score of the MIS group was significantly higher.

In vitro inhibition of aggrecanase activity by tetracyclines and proteoglycan loss from osteoarthritic human articular cartilage.

Tetracyclines were reported to slow down the progression of cartilage damage both in an animal model of osteoarthritis (OA) and in humans. In search for the underlying mechanisms we examined whether tetracyclines possess an inhibitory potential on the activity of aggrecanases and inflammatory mediators and can thus prevent proteoglycan (PG) loss from human articular cartilage. In vitro activity of aggrecanase-1 and -2 was recorded in the presence of 1-100 microM tetracycline, minocycline, or doxycyline. Human knee articular cartilage explants were sorted according to the degree of OA and treated for 10 days with tetracycline derivatives in the presence of interleukin-1 (IL-1beta). Synthesis and loss of PGs, nitric oxide (NO), and prostaglandin E(2) (PGE(2)), as well as the viability were determined. Tetracyclines derivatives dose-dependently inhibited the activities of both aggrecanases in vitro, whereas no inhibitory effect of tetracyclines on any proteoglycanolytic activities within IL-1beta-treated human cartilage explants were found. Tetracyclines can significantly modulate NO and PGE(2) levels, but have no effect on PG synthesis and loss within the same human cartilage explant cultures. Altogether, our data show that tetracyclines have no inhibitory potential on any proteoglycanolytic activities within mild or moderately affected human OA cartilage at therapeutic achievable plasma levels.

Range of motion after computed tomography-based simulation of intertrochanteric corrective osteotomy in cases of slipped capital femoral epiphysis: comparison of uniplanar flexion osteotomy and multiplanar flexion, valgisation, and rotational osteotomies.

BACKGROUND: Various osteotomy techniques have been developed to correct the deformity caused by slipped capital femoral epiphysis (SCFE) and compared by their clinical outcomes. The aim of the presented study was to compare an intertrochanteric uniplanar flexion osteotomy with a multiplanar osteotomy by their ability to improve postoperative range of motion as measured by simulation of computed tomographic data in patients with SCFE. METHODS: We examined 19 patients with moderate or severe SCFE as classified based on slippage angle. A computer program for the simulation of movement and osteotomy developed in our laboratory was used for study execution. According to a 3-dimensional reconstruction of the computed tomographic data, the physiological range was determined by flexion, abduction, and internal rotation. The multiplanar osteotomy was compared with the uniplanar flexion osteotomy. Both intertrochanteric osteotomy techniques were simulated, and the improvements of the movement range were assessed and compared. RESULTS: The mean slipping and thus correction angles measured were 25 degrees (range, 8-46 degrees) inferior and 54 degrees (range, 32-78 degrees) posterior. After the simulation of multiplanar osteotomy, the virtually measured ranges of motion as determined by bone-to-bone contact were 61 degrees for flexion, 57 degrees for abduction, and 66 degrees for internal rotation. The simulation of the uniplanar flexion osteotomy achieved a flexion of 63 degrees, an abduction of 36 degrees, and an internal rotation of 54 degrees. CONCLUSIONS: Apart from abduction, the improvement in the range of motion by a uniplanar flexion osteotomy is comparable with that of the multiplanar osteotomy. However, the improvement in flexion for the simulation of both techniques is not satisfactory with regard to the requirements of normal everyday life, in contrast to abduction and internal rotation. LEVEL OF EVIDENCE: Level III, Retrospective comparative study.

Femoral morphology due to impingement influences the range of motion in slipped capital femoral epiphysis.

Femoroacetabular impingement due to metaphyseal prominence is associated with the slippage in patients with slipped capital femoral epiphysis (SCFE), but it is unclear whether the changes in femoral metaphysis morphology are associated with range of motion (ROM) changes or type of impingement. We asked whether the femoral head-neck junction morphology influences ROM analysis and type of impingement in addition to the slip angle and the acetabular version. We analyzed in 31 patients with SCFE the relationship between the proximal femoral morphology and limitation in ROM due to impingement based on simulated ROM of preoperative CT data. The ROM was analyzed in relation to degree of slippage, femoral metaphysis morphology, acetabular version, and pathomechanical terms of "impaction" and "inclusion." The ROM in the affected hips was comparable to that in the unaffected hips for mild slippage and decreased for slippage of more than 30 degrees. The limitation correlated with changes in the metaphysic morphology and changed acetabular version. Decreased head-neck offset in hips with slip angles between 30 degrees and 50 degrees had restricted ROM to nearly the same degree as in severe SCFE. Therefore, in addition to the slip angle, the femoral metaphysis morphology should be used as criteria for reconstructive surgery.

Steady-state diffusion imaging for MR in-vivo evaluation of reparative cartilage after matrix-associated autologous chondrocyte transplantation at 3 tesla--preliminary results.

OBJECTIVES: To demonstrate the feasibility of time-reversed fast imaging with steady-state precession (FISP) called PSIF for diffusion-weighted imaging of cartilage and cartilage transplants in a clinical study. MATERIAL AND METHODS: In a cross-sectional study 15 patients underwent MRI using a 3D partially balanced steady-state gradient echo pulse sequence with and without diffusion weighting at two different time points after matrix-associated autologous cartilage transplantation (MACT). Mean diffusion quotients (signal intensity without diffusion-weighting divided by signal intensity with diffusion weighting) within the cartilage transplants were compared to diffusion quotients found in normal cartilage. RESULTS: The global diffusion quotient found in repair cartilage was significantly higher than diffusion values in normal cartilage (p<0.05). There was a decrease between the earlier and the later time point after surgery. CONCLUSIONS: In-vivo diffusion-weighted imaging based on the PSIF technique is possible. Our preliminary results show follow-up of cartilage transplant maturation in patients may provide additional information to morphological assessment.

Immunoscintigraphy of septic loosening of knee endoprosthesis: a retrospective evaluation of the antigranulocyte antibody BW 250/183.

Immunoscintigraphy with the use of the antigranulocyte antibody BW 250/183 is a reliable method for detecting infection, especially in septic loosening of hip prostheses, for which purpose quantitative interpretation of the time-activity course is employed. Therefore, we retrospectively studied whether similar results could be achieved in knee prostheses. We verified 28 scintigraphic examinations in 26 patients by histology. Scintigraphy was performed during an early (4-6 h post injection) and a late phase (23-25 h post injection). Infection was diagnosed when activity around the knee prosthesis increased by more than 10% compared with bone marrow. We found a sensitivity and a negative predictive value of 100%, a specificity of 80%, a positive predictive value of 81% and an accuracy of 89%. Specificity and accuracy are lower than in the evaluation of hip prostheses; however, in comparison to other scintigraphic modalities, scintigraphy with the antigranulocyte antibody BW 250/183 is superior in excluding infection and has better specificity and accuracy. Therefore, as in the case of hip prostheses, the described methodology appears to be the scintigraphic modality of choice for knee prostheses.