Osteoblast-specific overexpression of amphiregulin leads to transient increase in femoral cancellous bone mass in mice

The epidermal growth factor receptor ligand amphiregulin (AREG) has been implicated in bone physiology and in bone anabolism mediated by intermittent parathyroid hormone treatment. However, the functions of AREG in bone have been only incipiently evaluated in vivo. Here, we generated transgenic mice overexpressing AREG specifically in osteoblasts (Col1-Areg). pQCT analysis of the femoral metaphysis revealed increased trabecular bone mass at 4, 8, and 10 weeks of age in Col1-Areg mice compared to control littermates. However, the high bone mass phenotype was transient and disappeared in older animals. Micro-CT analysis of the secondary spongiosa confirmed increased trabecular bone volume and trabecular number in the distal femur of 4-week-old AREG-tg mice compared to control littermates. Furthermore, μ-CT analysis of the primary spongiosa revealed unaltered production of new bone trabeculae in distal femora of Col1-Areg mice. Histomorphometric analysis revealed a reduced number of osteoclasts in 4-week-old Col1-Areg mice, but not at later time points. Cancellous bone formation rate remained unchanged in Col1-Areg mice at all time points. In addition, bone mass and bone turnover in lumbar vertebral bodies were similar in Col1-Areg and control mice at all ages examined. Proliferation and differentiation of osteoblasts isolated from neonatal calvariae did not differ between Col1-Areg and control mice. Taken together, these data suggest that AREG overexpression in osteoblasts induces a transient high bone mass phenotype in the trabecular compartment of the appendicular skeleton by a growth-related, non-cell autonomous mechanism, leading to a positive bone balance with unchanged bone formation and lowered bone resorption.     

Strain shielding for cemented hip implants

BackgroundLong-term survival of hip implants is of increasing relevance due to the rising life expectancy. The biomechanical effect of strain shielding as a result of implant insertion may lead to bone resorption, thus increasing risk for implant loosening and periprosthetic fractures. Patient-specific quantification of strain shielding could assist orthopedic surgeons in choosing the biomechanically most appropriate prosthesis.MethodsValidated quantitative CT-based finite element models of five femurs in intact and implanted states were considered to propose a systematic algorithm for strain shielding quantification. Three different strain measures were investigated and the most appropriate measure for strain shielding quantification is recommended. It is used to demonstrate a practical femur-specific implant selection among three common designs.FindingsStrain shielding measures demonstrated similar trends in all Gruen zones except zone 1, where the volumetric strain measure differed from von-Mises and maximum principal strains. The volumetric strain measure is in better agreement with clinical bone resorption records. It is also consistent with the biological mechanism of bone remodeling so it is recommended for strain shielding quantification. Applying the strain shielding algorithm on three different implants for a specific femur suggests that the collared design is preferable. Such quantitative biomechanical input is valuable for practical patient specific implant selection.InterpretationVolumetric strain should be considered for strain shielding examination. The presented methodology may potentially enable patient-specific pre-operative strain shielding evaluation so to minimize strain shielding. It should be further used in a longitudinal study so to correlate between strain shielding predictions and clinical bone resorption.     

Intraoperative Practice Variability in Total Knee Arthroplasty

BackgroundConsiderable practice variability exists among orthopedic surgeons performing total knee arthroplasty (TKA). The purpose of this study is to understand what TKA surgical and perioperative techniques are standard among high-volume academic knee arthroplasty surgeons.MethodsA written survey with 59 questions regarding management preferences in TKA was distributed by the 2018 John N. Insall Traveling Fellows to all arthroplasty-trained attending physicians at 13 medical centers, with 45 responses recorded.ResultsSurveyed surgeons performed unicompartmental knee arthroplasty (88%) and bilateral TKA (87%). Most surveyed surgeons rarely or never performed outpatient primary TKA (71%). Conventional alignment guides and cemented implants were used by 80% of respondents. Most surgeons used posterior-stabilized implants (67%), followed by cruciate-retaining (20%), ultracongruent (20%), and medial congruent or medial pivot designs (17.8%). Surveyed surgeons frequently or always resurfaced the patella (73%), used a tourniquet for the entire case (73%), and used tranexamic acid for all TKAs (91%). The most common locations for intra-articular anesthetic injection were the arthrotomy (91%), the periosteum (84%), and the medial posterior capsule (82%). Saline (62%) and dilute iodine (47%) were the most common irrigation fluids. The arthrotomy was most commonly closed with running barbed suture (60%) followed by interrupted vicryl (40%). Skin closure was predominantly with running monocryl (60%) followed by staples (29%). Anticoagulation for TKA was primarily aspirin 81 mg BID (60%).ConclusionThere was considerable variability among surgeons polled although a strong preference for more conventional and less developmental techniques prevailed.