Christoph E. Albers

In vitro cytotoxicity of silver nanoparticles on osteoblasts and osteoclasts at antibacterial concentrations

Abstract Nanoparticulate silver coatings for orthopaedic implants promise to decrease postoperative infection rates. However, silver-induced cytotoxicity on bone cells has not been investigated in detail. This study investigated the cytotoxic effects of silver nano- and microparticles and Ag+ on osteoblasts (OBs) and osteoclasts (OCs) and correlated their effects with the antibacterial efficacy on Staphylococcus epidermidis. Silver nanoparticles (50 nm) exhibited strong cytotoxic effects on OBs and OCs. Weak cytotoxic effects were observed for silver microparticles (3 μm). The cytotoxicity was primarily mediated by a size-dependent release of Ag+. Antibacterial effects occurred at Ag+ concentrations that were 2–4 times higher than those inducing cytotoxic effects. Such adverse effects on OB and OC survival may have deleterious effects on the biocompatibility of orthopaedic implants. Our study represents an important step toward the detailed investigation of orthopaedic implant with nanoparticulate silver coatings prior to their widespread clinical usage.

Impingement Adversely Affects 10-year Survivorship After Periacetabular Osteotomy for DDH

BackgroundAlthough periacetabular osteotomy (PAO) for developmental dysplasia of the hip (DDH) provides conceptual advantages compared with other osteotomies and reportedly is associated with joint survivorship of 60% at 20 years, the beneficial effect of proper acetabular reorientation with concomitant arthrotomy and creation of femoral head-neck offset on 10-year hip survivorship remains unclear.Questions/purposesWe asked the following questions: (1) Does the 10-year survivorship of the hip after PAO improve with proper acetabular reorientation and a spherical femoral head; (2) does the Merle d’Aubigné-Postel score improve; (3) can the progression of osteoarthritis (OA) be slowed; and (4) what factors predict conversion to THA, progression of OA, or a Merle d’Aubigné-Postel score less than 15 points?MethodsWe retrospectively reviewed 147 patients who underwent 165 PAOs for DDH with two matched groups: Group I (proper reorientation and spherical femoral head) and Group II (improper reorientation and aspherical femoral head). We compared the Kaplan-Meier survivorship, Merle d’Aubigné-Postel scores, and progression of OA in both groups. A Cox regression analysis (end points: THA, OA progression, or Merle d’Aubigné-Postel score less than 15) was performed to detect factors predicting failure. The minimum followup was 10 years (median, 11 years; range, 10–14 years).ResultsAn increased survivorship was found in Group I. The Merle d’Aubigné-Postel score did not differ. Progression of OA in Group I was slower than in Group II. Factors predicting failure included greater age, lower preoperative Merle d’Aubigné-Postel score, and the presence of a Trendelenburg sign, aspherical head, OA, subluxation, postoperative acetabular retroversion, excessive acetabular anteversion, and undercoverage.ConclusionsProper acetabular reorientation and the creation of a spherical femoral head improve long-term survivorship and decelerate OA progression in patients with DDH.Level of EvidenceLevel III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Quantitative T2 mapping of the patella at 3.0T is sensitive to early cartilage degeneration, but also to loading of the knee.

Objective The aim of the study was to explore the sensitivity and robustness of T2 mapping in the detection and quantification of early degenerative cartilage changes at the patella. Materials and methods Forty-two patients (22 women, 20 men) with a mean age of 30.3 years and a symptomatic cartilage defect of ICRS grade ≤2 were examined using a 3 T MRI with an 8-channel knee coil. The cartilage lesion was graded based on high-resolution PD TSE and 3D isotropic TrueFISP images. T2 maps were calculated from a standard MESE-sequence, performed at the beginning and at the end of the scan (40 min in-between). Depending on the defect size, a region-of-interest (ROI) analysis was performed on 1–3 consecutive slices. Mean T2 values for the deep, superficial, and global layer as well as the zonal variation were compared among defect grades (ANOVA, post hoc Duncan-test) and over time (Students t-test). Results T2-measurements directly correlated with the extent of cartilage defect (ICRS grade) at all layers and at both time-points. However, correlations were closer for the second measurement at the end of the scan. In this unloaded state, differences in T2-values became more pronounced and were significant even between cartilage of normal appearance adjacent to the defect and healthy cartilage of control patients (both ICRS grade 0). In contrast, there were no such differences among grades in the zonal variation at any time. Conclusion T2 mapping might be a sensitive method for the detection of early cartilage degeneration at the patella in the unloaded joint.

LCPD: Reduced Range of Motion Resulting From Extra- and Intraarticular Impingement

BackgroundLegg-Calvé-Perthes disease (LCPD) often results in a deformity that can be considered as a complex form of femoroacetabular impingement (FAI). Improved preoperative characterization of the FAI problem based on a noninvasive three-dimensional computer analysis may help to plan the appropriate operative treatment.Questions/purposesWe asked whether the location of impingement zones, the presence of additional extraarticular impingement, and the resulting ROM differ between hips with LCPD and normal hips or hips with FAI.MethodsWe used a CT-based virtual dynamic motion analysis based on a motion algorithm to simulate the individual motion for 13 hips with LCPD, 22 hips with FAI, and 27 normal hips. We then determined the motion and impingement pattern of each hip for the anterior (flexion, adduction, internal rotation) and the posterior impingement tests (extension, adduction, external rotation).ResultsThe location of impingement zones in hips with LCPD differed compared with the FAI/normal groups. Intra- and extraarticular impingement was more frequent in LCPD (79% and 86%, respectively) compared with normal (15%, 15%) and FAI hips (36%, 14%). Hips with LCPD had decreased amplitude for all hip motions (flexion, extension, abduction, adduction, internal and external rotation) compared with FAI or normal.ConclusionsHips with LCPD show a decreased ROM as a result of a higher prevalence of intra- and extraarticular FAI. Noninvasive assessment of impingement characteristics in hips with LCPD may be helpful in the future for establishment of a surgical plan.

Femoroacetabular Impingement Predisposes to Traumatic Posterior Hip Dislocation

BackgroundTraumatic posterior hip dislocation in adults is generally understood to be the result of a high-energy trauma. Aside from reduced femoral antetorsion, morphologic risk factors for dislocation are unknown. We previously noticed that some hips with traumatic posterior dislocations had evidence of morphologic features of femoroacetabular impingement (FAI), therefore, we sought to evaluate that possibility more formally.Questions/purposesWe asked whether hips with a traumatic posterior hip dislocation present with (1) a cam-type deformity and/or (2) a retroverted acetabulum.MethodsWe retrospectively compared the morphologic features of 53 consecutive hips (53 patients) after traumatic posterior hip dislocation with 85 normal hips (44 patients) based on AP pelvic and crosstable axial radiographs. We measured the axial and the lateral alpha angle for detection of a cam deformity and the crossover sign, ischial spine sign, posterior wall sign, retroversion index, and ratio of anterior to posterior acetabular coverage to describe the acetabular orientation.ResultsHips with traumatic posterior traumatic dislocation were more likely to have cam deformities than were normal hips, in that the hips with dislocation had increased axial and lateral alpha angles. Hips with posterior dislocation also were more likely to be retroverted; dislocated hips had a higher prevalence of a positive crossover sign, ischial spine sign, and posterior wall sign, and they had a higher retroversion index and increased ratio of anterior to posterior acetabular coverage.ConclusionsHips with posterior traumatic dislocation typically present with morphologic features of anterior FAI, including a cam-type deformity and retroverted acetabulum. An explanation for these findings could be that the early interaction between the aspherical femoral head and the prominent acetabular rim acts as a fulcrum, perhaps making these hips more susceptible to traumatic dislocation.Level of EvidenceLevel III, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

Pelvic Morphology Differs in Rotation and Obliquity Between Developmental Dysplasia of the Hip and Retroversion

BackgroundDevelopmental dysplasia of the hip (DDH) and acetabular retroversion represent distinct acetabular pathomorphologies. Both are associated with alterations in pelvic morphology. In cases where direct radiographic assessment of the acetabulum is difficult or impossible or in mixed cases of DDH and retroversion, additional indirect pelvimetric parameters would help identify the major underlying structural abnormality.Questions/PurposesWe asked: How does DDH and retroversion differ with respect to rotation and coronal obliquity as measured by the pelvic width index, anterior inferior iliac spine (AIIS) sign, ilioischial angle, and obturator index? And what is the predictive value of each variable in detecting acetabular retroversion?MethodsWe reviewed AP pelvis radiographs for 51 dysplastic and 51 retroverted hips. Dysplasia was diagnosed based on a lateral center-edge angle of less than 20° and an acetabular index of greater than 14°. Retroversion was diagnosed based on a lateral center-edge angle of greater than 25° and concomitant presence of the crossover/ischial spine/posterior wall signs. We calculated sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve for each variable used to diagnose acetabular retroversion.ResultsWe found a lower pelvic width index, higher prevalence of the AIIS sign, higher ilioischial angle, and lower obturator index in acetabular retroversion. The entire innominate bone is internally rotated in DDH and externally rotated in retroversion. The areas under the ROC curve were 0.969 (pelvic width index), 0.776 (AIIS sign), 0.971 (ilioischial angle), and 0.925 (obturator index).ConclusionsPelvic morphology is associated with acetabular pathomorphology. Our measurements, except the AIIS sign, are indirect indicators of acetabular retroversion. The data suggest they can be used when the acetabular rim is not clearly visible and retroversion is not obvious.Level of EvidenceLevel III, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.

L51P — A BMP2 variant with osteoinductive activity via inhibition of Noggin

Bone morphogenetic proteins (BMP) have to be applied at high concentrations to stimulate bone healing. The limited therapeutic efficacy may be due to the local presence of BMP antagonists such as Noggin. Thus, inhibiting BMP antagonists is an attractive therapeutic option. We hypothesized that the engineered BMP2 variant L51P stimulates osteoinduction by antagonizing Noggin-mediated inhibition of BMP2. Primary murine osteoblasts (OB) were treated with L51P, BMP2, and Noggin. OB proliferation and differentiation were quantified with XTT and alkaline phosphatase (ALP) assays. BMP receptor dependent intracellular signaling in OB was evaluated with Smad and p38 MAPK phosphorylation assays. BMP2, Noggin, BMP receptor Ia/Ib/II, osteocalcin, and ALP mRNA expressions were analyzed with real-time PCR. L51P stimulated OB differentiation by blocking Noggin mediated inhibition of BMP2. L51P did not induce OB differentiation directly and did not activate BMP receptor dependent intracellular signaling via the Smad pathway. Treatment of OB cultures with BMP2 but not with L51P resulted in an increased expression of ALP, BMP2, and Noggin mRNA. By inhibiting the BMP antagonist Noggin, L51P enhances BMP2 activity and stimulates osteoinduction without exhibiting direct osteoinductive function. Indirect osteoinduction with L51P seems to be advantageous to osteoinduction with BMP2 as BMP2 stimulates the expression of Noggin thereby self-limiting its own osteoinductive activity. Treatment with L51P is the first protein-based approach available to augment BMP2 induced bone regeneration through inhibition of BMP antagonists. The described strategy may help to decrease the amounts of exogenous BMPs currently required to stimulate bone healing.

Inhibition of endogenous antagonists with an engineered BMP-2 variant increases BMP-2 efficacy in rat femoral defect healing

Bone morphogenetic proteins (BMP) have been used successfully by orthopedic clinicians to augment bone healing. However, these osteoinductive proteins must be applied at high concentrations to induce bone formation. The limited therapeutic efficacy may be due to the local expression of BMP antagonists such as Noggin that neutralize exogenous and endogenous BMPs. If so, inhibiting BMP antagonists may provide an attractive option to augment BMP induced bone formation. The engineered BMP-2 variant L51P is deficient in BMP receptor type I binding, but maintains its affinity for BMP receptor type II and BMP antagonists including Noggin, Chordin and Gremlin. This modification makes L51P a BMP receptor-inactive inhibitor of BMP antagonists. We implanted β-tricalcium phosphate ceramics loaded with BMP-2 and/or L51P into a critical size defect model in the rat femur to investigate whether the inhibition of BMP antagonist with L51P enhances the therapeutic efficacy of exogenous BMP-2. Our study reveals that L51P reduces the demand of exogenous BMP-2 to induce bone healing markedly, without promoting bone formation directly when applied alone.

Hip Pain in the Young Adult

In our experience, hip pain in the young adult is most often related to mechanical disorders, typically femoro-acetabular impingement or hip dysplasia. This article gives an overview on the underlying pathomechanical concepts, the diagnostic methods and the treatment options. In addition, the results of the various treatments are shortly presented and commented.

What Are the Risk Factors for Revision Surgery After Hip Arthroscopy for Femoroacetabular Impingement at 7-year Followup?

BackgroundIn recent years, surgical treatment of symptomatic femoroacetabular impingement (FAI) has been increasingly performed using arthroscopy. Bony pathomorphologies and damage to the labrum as well as cartilage defects can be addressed with comparable results to open surgery with overall less surgery-related complications. Despite the increasing importance of hip arthroscopy, however, reports on midterm clinical and radiographic outcomes and comparison to open surgical hip dislocation are scarce.Questions/purposes(1) What are the clinical and radiographic outcomes at a mean 7-year followup; (2) what is the cumulative 7-year survivorship, using the endpoints of THA, progression of osteoarthritis according to Tönnis, or poor clinical outcome with a Merle d’Aubigné score of less than 15 points, of hips with symptomatic FAI treated arthroscopically; and (3) what factors were associated with revision surgery?MethodsBetween 2003 and 2008 we performed a total of 62 arthroscopic procedures (60 patients) for FAI. For the same indication, we also performed 571 surgical hip dislocations during that time. Standardized treatment was femoral offset correction, acetabular rim trimming, or both and treatment of labral or chondral defects. An arthroscopic approach was generally used if the pathomorphology was located in the anterosuperior quadrant of the hip and was gradually used for more complex cases. We excluded 10 hips (10 patients) in which the standardized treatment was not achieved and no offset correction or acetabular rim trimming was performed. Of the remaining 52 hips (50 patients), 39 hips underwent isolated femoral offset correction, four hips isolated acetabular rim trimming, and nine hips both procedures. At a mean followup of 7 years (range, 5–11 years), the Merle d’Aubigné clinical score was obtained and plain radiographs were examined (Tönnis grade, heterotopic ossification, lateral center-edge [LCE] angle, acetabular index [AI], extrusion index, alpha angle, and pistol grip deformity). Cumulative survivorship was calculated according to Kaplan-Meier using conversion to THA, progression of osteoarthritis (one or more Tönnis grades), or poor clinical outcome (Merle d’Aubigné score < 15 points) as endpoints. Cox regression analysis was used to identify univariate factors associated with revision surgery.ResultsAt last followup we detected a significant but possibly not clinically relevant increase in Merle d’Aubigné scores from preoperative levels to latest followup (14 ± 1 versus 16 ± 2, mean difference 2 points with a 95% confidence interval [95% CI] −3 to 7, p < 0.001). Six hips showed progression of osteoarthritis. Cumulative survivorship (hips free from conversion to THA, progression of osteoarthritis, or poor clinical outcome) of hips treated with hip arthroscopy for FAI at a mean followup of 7 years was 81% (95% CI, 68%–95%). Two patients (two hips, 4%) underwent THA at 7 and 9 years, respectively. An increased preoperative acetabular coverage (LCE angle, AI), increased offset in the superior portion of the femoral neck (pistol grip deformity), and a remaining pistol grip deformity postoperatively were associated with revision surgery. Any treatment of the labrum did not influence the outcome. Factors associated with failure could not be identified.ConclusionsIn this series of patients with arthroscopic treatment of symptomatic FAI, hip arthroscopy resulted in an intact hip without progression of osteoarthritis and with a Merle d’Aubigné score of ≥ 15 points in 81% of patients at 7-year followup. Increased acetabular coverage and femoral pistol grip deformity were risk factors for revision surgery.Level of EvidenceLevel IV, therapeutic study.