Osseous metastases: drugs that enhance bone integrity and prevent adverse skeletal events

More than 400,000 cancer patients in the USA contend with bone metastases on an annual basis. These patients often suffer pain, a decline in quality of life, and a shortened survival. As a result, over the past several years, efforts to enhance bone integrity in patients with osseus metastases have become a major research priority. This review discusses the evolving role of bisphosphonates and their side effects, highlights other pharmacological interventions aimed at enhancing bone integrity, and reviews other pragmatic approaches to prevent worsening pain and fractures, as derived from a single institution case series of patients with problematic rib metastases.     

骨性III类错患者双颌术后面部各区域软组织三维改变的研究

目的 探究骨性Ⅲ类错畸形患者双颌手术后面部各区域软组织的变化特点。 方法 2017—2019年于我院就诊的18例骨性Ⅲ类错畸形患者，男女各9例。使用3dMD摄影测量系统分别于双颌手术前一周内任一天和术后6个月拍摄患者面部图像，并通过Geomagic Qualify软件对手术前后的面部图像进行三维重建和匹配，分割各个面部区域，得出面部各区域软组织的变化量。 结果 术后颞区（R1）软组织改变量为-0.17 mm,颧弓区（R4）为-0.42 mm,下口角旁区（R11）为-0.81 mm，下唇及颏区（M3）为-3.08 mm，呈负向改变（P＜0.05）；眶下区（R2）软组织改变量为0.29 mm，鼻翼旁区（R5）为1.58 mm，上口角旁区（R8）1.08 mm，鼻区（M1）为0.59 mm，上唇区（M2）为2.05 mm，呈正向改变（P＜0.05）；左右两侧相同面部区域的软组织变化无统计学差异（P>0.05）；同区域男性与女性的软组织变化差异无统计学意义（P>0.05）。 结论 骨性Ⅲ类错畸形患者双颌手术后颞区、颧弓区、下口角旁区、下唇及颏区的软组织变得凹陷，而眶下区、鼻翼旁区、上口角旁区、鼻区、上唇区的软组织变得凸出。术后左右侧相同面部区域的软组织改变无差异，性别对术后面部各区域软组织的改变没有影响。     

Deletion of mouse Porcn blocks Wnt ligand secretion and reveals an ectodermal etiology of human focal dermal hypoplasia/Goltz syndrome

The Drosophila porcupine gene is required for secretion of wingless and other Wnt proteins, and sporadic mutations in its unique human ortholog, PORCN, cause a pleiotropic X-linked dominant disorder, focal dermal hypoplasia (FDH, also known as Goltz syndrome). We generated a conditional allele of the X-linked mouse Porcn gene and analyzed its requirement in Wnt signaling and embryonic development. We find that Porcn-deficient cells exhibit a cell-autonomous defect in Wnt ligand secretion but remain responsive to exogenous Wnts. Consistent with the female-specific inheritance pattern of FDH, Porcn hemizygous male embryos arrest during early embryogenesis and fail to generate mesoderm, a phenotype previously associated with loss of Wnt activity. Heterozygous Porcn mutant females exhibit a spectrum of limb, skin, and body patterning abnormalities resembling those observed in human patients with FDH. Many of these defects are recapitulated by ectoderm-specific deletion of Porcn, substantiating a long-standing hypothesis regarding the etiology of human FDH and extending previous studies that have focused on downstream elements of Wnt signaling, such as β-catenin. Conditional deletion of Porcn thus provides an experimental model of FDH, as well as a valuable tool to probe Wnt ligand function in vivo.     

Purine Metabolism During Microsurgical Transfer of Human Skeletal Muscle

The effect of ischaemia followed by reperfusion on energy metabolism was studied in human skeletal muscle after microsurgical free transfer. Muscle biopsy specimen from 11 patients treated by free muscle transfer for facial palsy, injury to an extremity, or scalp defect were studied. The biopsy specimens were taken during ischaemia and after one hour of reperfusion, respectively. They were analysed for ATP to uric acid and creatine phosphate by high pressure liquid chromatography. Ischaemia lasting one or two hours affected the energy metabolism of the muscle cell as evidenced by a 50% reduction in creatine phosphate; a 20% reduction in ATP and in the energy charge; a 100% increase in inosine monophosphate, and a 700% increase in hypoxanthine and xanthine. Reperfusion for one hour improved these figures somewhat, and induced the production of uric acid. Skeletal muscle can therefore tolerate ischaemia for up to two hours in the clinical situation without permanent damage to the tissues.     

The Significance of Calcified Fibrocartilage on the Cortical Endplate of the Translational Sheep Spine Model

To gain an understanding of the vertebral cortical endplate and factors that may affect the ability to achieve skeletal attachment to intervertebral implants and fusion, this study aimed to characterize the hypermineralized tissue on the cortical endplate of the vertebral body on a commonly used animal model. Skeletally mature sheep were injected with tetracycline prior to euthanasia and the C2‐C3, T5‐T6, and L2‐L3 spinal motion segments were excised and prepared. Vertebral tissues were imaged using backscatter electron (BSE) imaging, histology, and tetracycline labeling was used to assess bone remodeling within different tissue layers. It was determined that the hypermineralized tissue layer was calcified fibrocartilage (CFC). No tetracycline labels were identified in the CFC layer, in contrast to single and double labels that were present in the underlying bone, indicating the CFC present on the cortical endplate was not being actively remodeled. The average thickness of the CFC layer was 146.3 ± 70.53 µm in the cervical region, 98.2 ± 40.29 µm in the thoracic region, and 150.89 ± 69.25 µm in the lumbar region. This difference in thickness may be attributed to the regional biomechanical properties of the spine. Results from this investigation indicate the presence of a nonremodeling tissue on the cortical endplate of the vertebral body in sheep spines, which attaches the intervertebral disc to the vertebrae. This tissue, if not removed, would likely prevent successful bony attachment to an intervertebral device in spinal fusion studies and total disc replacement surgeries. Anat Rec, 296:736–744, 2013. © 2013 Wiley Periodicals, Inc.     

Chest wall deformity after tissue expansion

There have been few reports about skeletal changes beneath a tissue expander in breast reconstruction. We present one, and surgeons should be cautious about the possibility of skeletal deformities in patients who are osteoporotic and postmenopausal who require prolonged tissue expansion.