Activation of Protein Kinase A in Mature Osteoblasts Promotes a Major Bone Anabolic Response.

Protein kinase A (PKA) regulates osteoblast cell function in vitro and is activated by important bone mass modulating agents. We determined whether PKA activation in osteoblasts is sufficient to mediate a bone anabolic response. Thus, a mouse model conditionally expressing a constitutively active PKA (CA-PKA) in osteoblasts (CA-PKA-OB mouse) was developed by crossing a 2.3-kb α1 (I)-collagen promoter-Cre mouse with a floxed-CA-PKA mouse. Primary osteoblasts from the CA-PKA-OB mice exhibited higher basal PKA activity than those from control mice. Microcomputed tomographic analysis revealed that CA-PKA-OB female mice had an 8.6-fold increase in femoral but only 1.16-fold increase in lumbar 5 vertebral bone volume/total volume. Femur cortical thickness and volume were also higher in the CA-PKA-OB mice. In contrast, alterations in many femoral microcomputed tomographic parameters in male CA-PKA-OB mice were modest. Interestingly, the 3-dimensional structure model index was substantially lower both in femur and lumbar 5 of male and female CA-PKA-OB mice, reflecting an increase in the plate to rod-like structure ratio. In agreement, femurs from female CA-PKA-OB mice had greater load to failure and were stiffer compared with those of control mice. Furthermore, the CA-PKA-OB mice had higher levels of serum bone turnover markers and increased osteoblast and osteoclast numbers per total tissue area compared with control animals. In summary, constitutive activation of PKA in osteoblasts is sufficient to increase bone mass and favorably modify bone architecture and improve mechanical properties. PKA activation in mature osteoblasts is, therefore, an important target for designing anabolic drugs for treating diseases with bone loss.

Glenoid implant orientation and cement failure in total shoulder arthroplasty: a finite element analysis.

BACKGROUND: To minimize glenoid implant loosening in total shoulder arthroplasty (TSA), the ideal surgical procedure achieves correction to neutral version, complete implant-bone contact, and bone stock preservation. These goals, however, are not always achievable, and guidelines to prioritize their impact are not well established. The purpose of this study was to investigate how the degree of glenoid correction affects potential cement failure. METHODS: Eight patient-specific computer models were created for 4 TSA scenarios with different permutations of retroversion correction and implant-bone contact. Two bone models were used: a homogeneous cortical bone model and a heterogeneous cortical-trabecular bone model. A 750-N load was simulated, and cement stress was calculated. The risk of cement mantle fracture was reported as the percentage of cement stress exceeding the material endurance limit. RESULTS: Orienting the glenoid implant in retroversion resulted in the highest risk of cement fracture in a homogeneous bone model (P < .05). In the heterogeneous bone model, complete correction resulted in the highest risk of failure (P = .0028). A positive correlation (ρ = 0.901) was found between the risk of cement failure and amount of exposed trabecular bone. CONCLUSIONS: Incorporating trabecular bone into the model changed the effect of implant orientation on cement failure. As exposed trabecular bone increased, the risk of cement fracture increased. This may be due to shifting the load-bearing support underneath the cement from cortical bone to trabecular bone.

Glenoid morphology after reaming in computer-simulated total shoulder arthroplasty.

BACKGROUND: The relationships between reaming parameters for glenoid-implant surface area and bone loss in total shoulder arthroplasty have not been well established. The hypotheses of this study are: (1) for large version corrections, a large reaming depth of 5 mm is not sufficient to obtain complete glenoid implant contact; (2) glenoid bone is removed in a linear proportion with reaming depth; and (3) initial reamer placement has no effect on glenoid bone removal. METHODS: Ten computer models from computed tomography scans of patients with advanced osteoarthritis were created for computer-simulated reaming as performed during total shoulder arthroplasty. Reaming variables studied included reaming depth, reamer placement, and version correction. The resulting reamed glenoid surface area available for implantation and bone volume removed were calculated for each permutation. RESULTS: Reamed surface area significantly increased with larger depths of reaming (P < .0001) and smaller version corrections (P < .0001). Bone volume removed and reaming depth had a strong quadratic relationship (r(2) = 0.999). With off-center reamer placement, volume removed when deviating in the posterior direction was significantly greater than when deviating in the anterior, superior, or inferior direction (P < .05). CONCLUSION: Performing smaller version corrections allows for greater attainable implant-bone surface contact because increasing reaming depth results in small increases in conforming surface area but large losses in glenoid bone stock. Bone volume removed was most sensitive to off-center position errors in the posterior direction.

Glenoid articular conformity affects stress distributions in total shoulder arthroplasty.

BACKGROUND: The stress applied to the glenoid component in total shoulder arthroplasty (TSA) remains an important concern because of the risk of wear and loosening. The purpose of this study was to determine the stress pattern in the glenoid component with 3 different surface designs. METHODS: Computer models of 9 scapulae of patients scheduled for TSA were created from computerized tomography images. Each glenoid was virtually reamed, and 3 different glenoid component designs (conforming, nonconforming, and hybrid) were placed. Using finite element analysis, superior translation of the humeral head was modeled. Maximum stress and shear stress were measured at 3 different locations in the glenoid component: center, transition, and superior regions. RESULTS: All 3 designs showed a similar level of maximum stress at the center and transition regions, while the maximum stress at the superior periphery was significantly higher in the conforming design than in the other 2 designs (P = .0017). The conforming design showed significantly higher shear stress at the superior periphery (P < .0001). DISCUSSION: Stress from periphery loading is higher than from the center and transition region regardless of component design and is highest in the conforming design. The stress at the transition region of the hybrid design was not higher than the other 2 designs. The hybrid design has favorable characteristics based on its low stress at the periphery and greater contact area with the humeral head at the center. LEVEL OF EVIDENCE: Basic Science Study, Biomechanical Computer Simulation Study.

Effects of single-bundle and double-bundle ACL reconstruction on tibiofemoral compressive stresses and joint kinematics during simulated squatting.

The purpose of this study was to compare tibiofemoral (TF) kinematics and TF compressive stresses between single bundle- (SB-) and double bundle-ACL reconstruction (DB-ACLR) during simulated squatting. Twelve matched pairs of fresh frozen cadaver knees were utilized. A simulated squat through 100° of knee flexion was performed in the ACL-intact joint. The ACL was transected and SB- and DB-ACLR procedures were performed in one knee of each pair. The squat was repeated. Knee kinematics were measured using a motion tracking system and the TF compressive forces were measured using thin film pressure sensors. The posterior shifts of the tibia for SB- and DB-ACLR knees were significantly greater than the ACL-intact condition for knee flexion angles 0° to 40° (p<.05). However, there was no difference between the SB- and DB-ACLR knees at any flexion angle (0° to 100°; p=.37). SB- and DB-ACLR knees had greater IE rotation than intact knees from 90° through 50° of flexion (p<.05), but not between 40° and full extension. There was no difference between SB- and DB-ACLR knees (p=.68). The TF compressive stresses of the DB-ACLR were significantly lower than intact for all angles except 10° (p=.06), whereas SB-ACLR knees did not differ from intact at flexion angles between 30° and 50° (p>.32). There were no significant differences between the two reconstruction conditions (p=.74). This study showed that there was no difference in the TF kinematics or compressive stresses between SB- and DB-ACLR, and only minor differences when compared to the intact state.

Biomechanical evaluation of shear force vectors leading to injury of the biceps reflection pulley: a biplane fluoroscopy study on cadaveric shoulders.

BACKGROUND: The clinical importance of the biceps reflection pulley (BRP), which stabilizes the long head of the biceps tendon (LHB) as it exits the joint, has been shown. However, there is controversy on the pathomechanism of injury to the BRP. The angular orientation of the LHB relative to its origin and distal course changes with joint positions and may place the BRP at risk for injury. PURPOSE: To measure the course of the LHB in common arm positions and to determine the shear and normal (stabilizing) force vectors as well as the excursion of the LHB. STUDY DESIGN: Descriptive laboratory study. METHODS: The LHBs of 8 fresh-frozen cadaveric shoulders were marked with arthroscopically injected microbeads and mounted in a custom-built shoulder rig. Data for neutral arm position, forward flexion, and abduction were collected in internal, neutral, and external rotation using biplane fluoroscopy. Bone and LHB position were reconstructed in 3 dimensions. RESULTS: The shear component of the resulting vector was significantly higher during internal (28.4% +/- 18.1%) compared with external rotation (18.9% +/- 9.7%; P = .0157) and was highest in neutral arm position with internal rotation (39.2% +/- 12.7%) and forward flexion with neutral rotation (36.2% +/- 10.7%). The normal force vector, stabilizing the LHB, was significantly higher in abduction (55.2% +/- 9.6%) compared with forward flexion (39.1% +/- 12.4%; P <.0001) and neutral positions (39.1% +/- 11.4%; P <.0001). The LHB excursion was significantly lower for neutral arm positions (0.7 +/- 6.0 mm) compared with forward flexion (12.6 +/- 8.3 mm; P <.0001) and abduction (12.0 +/- 6.5 mm; P <.0001). CONCLUSION: Increased shear load at forward flexion with internal or neutral arm rotation and internal rotation at neutral arm position may cause injury to the BRP. Additionally, a sawing mechanism caused by the 12-mm linear excursion combined with a load of the LHB through the BRP during elevation may also lead to lesions. CLINICAL RELEVANCE: Knowledge of the pathomechanisms of BRP injury may help in developing specific treatment and rehabilitation strategies as well as tests for physical examination.