Ecto-5′-nucleotidase (CD73) generates adenosine, an osteoblast activator and key regulator of skeletal growth. It is unknown, however, if CD73 regulates osteogenic differentiation during fracture healing in adulthood, and in particular how CD73 activity regulates intramembranous bone repair in the elderly by using a CD73 knock-out (CD73−/−) mouse model. Monocortical tibial defects were created in 46 to 52-week-old wild type (WT) and CD73−/− mice. Injury repair was analyzed at post-operative days 5, 7, 14 and 21 by micro-computed tomography (micro-CT), histomorphometry, proliferating cell nuclear antigen (PCNA) immunostaining, alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) histochemistry. Aged CD73 knock-out mice exhibited delayed bone regeneration and significantly reduced bone matrix deposition during bone healing detected by histomorphometry and micro-CT. Cell proliferation, ALP activity and osteoclast number were reduced in the CD73−/− mice, suggesting a combined defect in bone formation and resorption due the absence of CD73 activity in this model of intramembranous bone repair. Results from this study demonstrate that osteoblast activation through CD73 activity is essential during bone repair in aged mice, and it may present a drugable target for future biomimetic therapeutic approaches that aim at enhancing bone formation in the elderly patients.

Owing to the central role of osteoclasts in bone physiology and remodeling, manipulation of their maturation process provides a potential therapeutic strategy for treating bone diseases. To investigate this, we genetically inhibited the Notch signaling pathway in the myeloid lineage, which includes osteoclast precursors, using a dominant negative form of MAML (dnMAML) that inhibits the transcriptional complex required for downstream Notch signaling. Osteoclasts derived from dnMAML mice showed no significant differences in early osteoclastic gene expression compared to the wild type. Further, these demonstrated significantly lowered resorption activity using bone surfaces while retaining their osteoblast stimulating ability using ex vivo techniques. Using in vivo approaches, we detected significantly higher bone formation rates and osteoblast gene expression in dnMAML cohorts. Further, these mice exhibited increased bone/tissue mineral density compared to wild type and larger bony calluses in later stages of fracture healing. These observations suggest that therapeutic suppression of osteoclast Notch signaling could reduce, but not eliminate, osteoclastic resorption without suppression of restorative bone remodeling and, therefore, presents a balanced paradigm for increasing bone formation, regeneration, and healing. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2089–2103, 2019

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Intramuscular vaccinations are a necessary tool in the prevention of communicable disease in the public health realm. While commonplace, these vaccinations have the potential for adverse side effects and complications. While local skin reactions are the major cause of morbidity associated with immunizations, other more significant problems can arise. These problems can be secondary to the vaccine itself and/or the technique of administration. We present a rare and previously undescribed case of a vaccination induced rotator cuff tear occurring as the direct result of an inadvertent administration of a TDaP vaccine into the insertion of the infraspinatus and teres minor tendons on the posterior aspect of the greater tuberosity.

Anterior cruciate ligament injury affects roughly 120,000 athletes in the United States every year. One of the most common techniques is the use of a bone-patellar tendon-bone graft. Graft harvest creates a sizeable defect in the remaining patellar tendon. Closure of this defect is based on surgeon preference. To date there has been no study on the effects of defect closure on the mechanical properties of remaining donor patellar tendon. The goal of this study was to investigate the effect of closure on both the strength and stiffness of the remaining patellar tendon. 7 pairs of fresh frozen cadaver patellar tendons were matched by tendon dimensions. Bone-patellar tendon-bone grafts were harvested from all of the specimens and then half of the paired tendons underwent defect closure. All of the donor tendons were then tested in a servohydraulic load frame to failure at a constant displacement rate at room temperature. This study found no differences in the load at failure, the engineering failure stress, stiffness or in the engineering modulus between the donor tendons that underwent defect closure versus those that did not.