Orchiectomy sensitizes cortical bone in male mice to the harmful effects of kynurenine.

Kynurenine (Kyn) is a tryptophan metabolite that increases with age and promotes musculoskeletal dysfunction. We previously found a sexually dimorphic pattern in how Kyn affects bone, with harmful effects more prevalent in females than males. This raises the possibility that male sex steroids might exert a protective effect that blunts the effects of Kyn in males. To test this, orchiectomy (ORX) or sham surgeries were performed on 6-month-old C57BL/6 mice, after which mice received Kyn (10 mg/kg) or vehicle via intraperitoneal injection, once daily, 5×/week, for four weeks. Bone histomorphometry, DXA, microCT, and serum marker analyses were performed after sacrifice. In vitro studies were performed to specifically test the effect of testosterone on activation of aryl hydrocarbon receptor (AhR)-mediated signaling by Kyn in mesenchymal-lineage cells. Kyn treatment reduced cortical bone mass in ORX- but not sham-operated mice. Trabecular bone was unaffected. Kyn's effects on cortical bone in ORX mice were attributed primarily to enhanced endosteal bone resorption activity. Bone marrow adipose tissue was increased in Kyn-treated ORX animals but was unchanged by Kyn in sham-operated mice. ORX surgery increased mRNA expression of the aryl hydrocarbon receptor (AhR) and its target gene Cyp1a1 in the bone, suggesting a priming and/or amplification of AhR signaling pathways. Mechanistic in vitro studies revealed that testosterone blunted Kyn-stimulated AhR transcriptional activity and Cyp1a1 expression in mesenchymal-linage cells. These data suggest a protective role for male sex steroids in blunting the harmful effects of Kyn in cortical bone. Therefore, testosterone may play an important role in regulating Kyn/AhR signaling in musculoskeletal tissues, suggesting crosstalk between male sex steroids and Kyn signaling may influence age-associated musculoskeletal frailty.

Posttraumatic Soft Tissue Coverage of the Lower Leg for the Orthopedic Surgeon.

Soft tissue reconstructive techniques are powerful tools for the orthopedic surgeon caring for lower extremity trauma. This article seeks to inform orthopedic surgeons about useful techniques for skin closure, secondary wound closure techniques, and rotational flaps of the lower leg. Split thickness skin grafting, piecrusting, and the use of negative pressure wound therapy for skin closure, as well as rotational gastrocnemius, soleus, and reverse sural artery flaps are discussed with emphasis on techniques for the nonvascular and nonmicrovascular orthopedic surgeon.

Anaplastic Lymphoma Kinase (ALK)-Negative Inflammatory Myofibroblastic Tumor of the Kidney in a Nine-Month-Old Girl.

An inflammatory myofibroblastic tumor (IMT) is an uncommon, benign tumor of myofibroblastic spindle cells. An IMT can occur in any part of the body. However, involving kidney is exceedingly rare. When this rare entity occurs in children, it becomes incredibly challenging to distinguish this rare entity from other malignancies such as Wilms tumor. Although imaging studies of the abdomen and pelvis add to the diagnosis, however, histological examination and immunohistochemical staining remain the gold standard for the precise diagnosis of this rare entity. To the best of our knowledge, only 48 cases of renal IMT have been published in the medical literature so far. We report the case of a nine-month-old girl who was brought with complaints of hematuria, and later, imaging and histological confirmation revealed an anaplastic lymphoma kinase (ALK)-negative IMT of the kidney.