PubMed Health⌕ Search

Biomedical subjects

D von Stechow

Publications and source records attributed to D von Stechow.

5 recordsLinked to original sources

Differential transcriptional effects of PTH and estrogen during anabolic bone formation.

The aim of this study was to compare transcriptional regulation in vivo during anabolic bone formation induced by either estradiol (E2) treatment or intermittent parathyroid hormone[1-34] (PTH) therapy. We utilized an ovariectomized (OVX) mouse model of osteoporosis and transcriptional profiling to identify genes upregulated by either high-dose E2 or PTH. Five weeks post-OVX, the mice were administered either E2 and/or PTH, or vehicle for 4 weeks. Femoral bones were analyzed by microCT and histomorphometry to confirm the anabolic effect of each treatment. OVX vehicle-treated control mice lost metaphyseal trabecular bone, with significant decrease in trabecular number, thickness, and connectivity. Both E2 and PTH treatments increased trabecular and cortical bone indices above the level of the sham operated controls, fully restoring both bone volume and bone mineral density (BMD). Moreover, PTH/E2 combination treatment led to significantly greater increase in cancellous bone and BMD than would be expected from the additive effects of the separate treatments. To determine whether PTH and E2 treatments were stimulating similar bone anabolic mechanisms, or were activating distinct signaling pathways, we compared patterns of gene expression using transcriptional profiling after either E2 or PTH treatment. After 4, 11, and 24 days of treatment, total RNA was collected from both the distal femoral metaphysis and diaphysis. Transcriptional profiling was performed using Affymetrix GeneChip probe arrays, comprised of approximately 36,000 full-length mouse genes and EST clusters from the UniGene database. Several markers of osteoblast activity, including c-fos, RANKL, PHEX, and PTHR1, were consistently upregulated by PTH in both skeletal sites. PTH treatment also increased expression of Cathespin K, consistent with the predicted increase in osteoclast activity. E2 treatment upregulated a largely distinct set of genes, including TGFbeta3, and BMP1, as well as several genes critical for cell cycle control, including Cyclin D1 and CDK inhibitor 1A. Overall, comparison of transcriptional profiles suggest that anabolic responses in bone to PTH and high-dose E2 treatment after OVX-induced osteoporosis involve largely distinct patterns of gene regulation, each resulting in restoration of bone mass.

Absorptiometry, Photon↗

[Complications of vertebroplasty].

Percutaneous vertebroplasty was first introduced in 1984 by Galibert et al. for the treatment of hemangiomas in the spine. The current indications for vertebroplasty also include compression fractures due to osteoporosis as well as osteolytic metastases and spinal myeloma lesions. With the numbers of percutaneous vertebroplasty performed by orthopedic and trauma surgeons, neurosurgeons, and radiologists steadily increasing, complications have also risen. Over the last 3 years an increasing number of cases with varying complications, their genesis, and their management have been reported in the literature. Complications include asymptomatic cement leakage, cardiovascular effects, embolism with lethal outcome as well as severe neurological deficits. This article presents a review of the complications reported in the literature, strategies for preventing possible complications as well as current concepts in therapy management. Several of our cases with cement leakages are presented.

Bone Cements↗

[Drug therapy of back pain].

The importance of analgesic drugs in the treatment of low back pain is a matter of intense debate. Based on the current literature, a multidisciplinary approach combining drug treatment with physical and psychotherapy has proven to be the most successful treatment of back pain. This perspective is challenged by various anesthesiologists who claim that early use of opioids in back pain therapy is the concept of choice. The results of recent studies regarding this matter are controversial. This chapter reviews the historical background of analgetic drugs and provides an overview of the current diagnostic and therapeutic options in the treatment of back pain. Recommendations are given based on the results of current randomized controlled studies.

Analgesics↗

[Intra-articular injection. Substances and techniques].

Intra-articular injections are widely used in the treatment of joint pain and/or inflammation. Low costs, effectiveness, and safety are offered as possible reasons. The method remains controversial, as the evidence supporting the efficacy of these procedures has been poor. To evaluate intra-articular therapy, a meta-analysis of the efficacy of various agents injected intra-articularly was performed. Furthermore, indications and medications are discussed.

Adjuvants, Immunologic↗

TRANCE/RANKL knockout mice are protected from bone erosion in a serum transfer model of arthritis.

There is considerable evidence that osteoclasts are involved in the pathogenesis of focal bone erosion in rheumatoid arthritis. Tumor necrosis factor-related activation-induced cytokine, also known as receptor activator of nuclear factor-kappaB ligand (TRANCE/RANKL) is an essential factor for osteoclast differentiation. In addition to its role in osteoclast differentiation and activation, TRANCE/RANKL also functions to augment T-cell dendritic cell cooperative interactions. To further evaluate the role of osteoclasts in focal bone erosion in arthritis, we generated inflammatory arthritis in the TRANCE/RANKL knockout mouse using a serum transfer model that bypasses the requirement for T-cell activation. These animals exhibit an osteopetrotic phenotype characterized by the absence of osteoclasts. Inflammation, measured by clinical signs of arthritis and histopathological scoring, was comparable in wild-type and TRANCE/RANKL knockout mice. Microcomputed tomography and histopathological analysis demonstrated that the degree of bone erosion in TRANCE/RANKL knockout mice was dramatically reduced compared to that seen in control littermate mice. In contrast, cartilage erosion was present in both control littermate and TRANCE/RANKL knockout mice. These results confirm the central role of osteoclasts in the pathogenesis of bone erosion in arthritis and demonstrate distinct mechanisms of cartilage destruction and bone erosion in this animal model of arthritis.

Animals↗