Delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) in Femoacetabular impingement

Femoroacetabular impingement is a well-described pre-arthritic condition with two main types; cam and pincer. Studies using the open treatment for impingement have described patterns of articular cartilage wear specific to cam and pincer impingement. Assessing articular damage in the hip joint is an important component of treatment. Intravenous gadolidium allows radiologists to perform an indirect assessment of articular cartilage glycosaminoglycan (GAG) content by using a technique called dGEMRIC. Using this indirect assessment of articular cartilage, we compared the dGEMRIC indices in a group of six cam and seven pincer patients to a control group (n = 12) of asymptomatic controls that had no plain MRI findings of osteoarthritis. The superior portion of the hip joint was divided into seven regions from 9 to 3 o'clock. These regions were then subdivided into peripheral and central regions. The cam and pincer groups both had statistically lower dGEMRIC values compared to the control group. The cam group demonstrated not only peripheral but also central involvement of the joint and this was concentrated in the anterior portion of the joint. The pincer group exhibited more global hip involvement with all areas of the hip averaging a dGEMRIC index 28% less than controls. With the use of dGEMRIC more specific patterns of cartilage wear can be elicited in patients with impingement, which may improve patient selection and help better understand the progression of osteoarthithis throughout the hip joint.

Pelvic morphology differs in rotation and obliquity between developmental dysplasia of the hip and retroversion

Developmental 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.

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.