摘要:

Control of osteoclastogenesis and osteoclast activity is critical for the treatment of metabolic bone diseases. The long sought after molecules that directly control the function and fate of these specialized bone-resorbing cells have recently been identified. Here we review the discovery of these molecules (receptor activator of nuclear factor &kgr;B/osteoclast differentiation and activation receptor; osteoclast differentiation factor/osteoprotegerin ligand/tumor necrosis factor–related activation-induced cytokine; and osteoprotegerin/osteoclast inhibitory factor) and thein vivopreclinical and clinical data supporting their role as dominant regulators of osteoclasts. These molecules are all members of the tumor necrosis factor receptor superfamily, which has been shown to regulate programmed cell death by either suppressing apoptosis via inducing the expression of survival genes, or initiating apoptosis through activation of the caspase cascade. In an attempt to explain the teleology of this signaling pathway and how it controls the osteoclast lifespan, we propose a model in which a loose analogy is drawn between this pathway and that of tumor necrosis factor signaling in T lymphocytes. Future experimentation to test this model will provide a better understanding of this pathway and information as to the best way to manipulate this system to treat patients with musculoskeletal disease.

ISSN:1041-9918    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Osteoporotic fractures continue to be common in the elderly population and very costly to the healthcare system. Prevention remains the mainstay of treatment. Adequate exercise and calcium intake should be encouraged in all age groups. The rate of bone turnover for patients who present with osteoporosis should be defined. Those patients should be started on medication to slow bone loss. Several pharmacologic therapies including estrogen and biphosphonates are currently available for treatment of osteopenia and osteoporosis. New research is investigating additional therapies that may stimulate osteoblasts to increase bone mass. Recent insights into the regulation of osteoclast function may lead to additional therapeutic approaches in the future.

ISSN:1041-9918    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Osteogenesis imperfecta (OI) is a group of heritable diseases of the connective tissues characterized by tissue fragility and skeletal deformities. Heterogeneous mutations in the genes encoding type I collagen underlie the majority of OI cases. The studies reviewed here highlight the potential for new therapeutic strategies, diagnostic techniques, molecular research, and characterization of bone tissue parameters across the spectrum of OI. Recent developments in genetic and molecular biologic approaches are providing new insights regarding OI pathogenesis, diagnosis, and treatment strategies. With respect to therapies, the use of bisphosphonates to treat OI appears to be the most promising for the short term. The potential for bone marrow transplants is also encouraging, but significant challenges need to be overcome before this can be considered as a universal clinical option.

ISSN:1041-9918    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Recent advances in molecular genetics have resulted in the identification of the underlying molecular causes of nearly all of the common forms of the human chondrodysplasias. Analysis of the normal functions of the proteins encoded by these mutated genes has vastly increased our knowledge of the normal biology of cartilage in general and of growth plate chondrocytes in particular. In some cases this new knowledge has resulted in the realization that diseases that were previously thought to be phenotypically distinct are part of a continuum of disorders resulting from mutations in the same gene. These new discoveries not only make prenatal diagnosis possible for many of these chondrodysplasias but also foreshadow the eventual correction of the molecular defect in cartilage cells through gene therapy approaches.

ISSN:1041-9918    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Bone metastasis is a leading cause of morbidity in cancer patients. Bone metastasis involves a complex series of biologic events but is ultimately dependent on cancer-mediated bone resorption. Recent advances have established a critical role for resident osteoclasts in this process. Furthermore, the paracrine interactions between cancer cells, resident stromal cells and osteoblasts, and cells in the osteoclast lineage have been defined along with the biologic mediators of these important interactions. These advances have provided novel targets to inhibit tumor-mediated bone resorption and have the potential to markedly decrease the morbidity of terminal cancer.

ISSN:1041-9918    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The skeleton is an important target for lead's toxic effects. During development lead will adversely affect growth plate cartilage metabolism and lead to a growth stunt. Lead exposure will also prevent attaining a high peak bone density. During early adulthood, lead is effectively sequestered in bone and likely plays a subclinical role in bone metabolism. However, increases in skeletal turnover in aging adults, especially postmenopausal females, leads to the release of lead stores from bone and contributes to toxic effects on osteoclasts and osteoblasts. This paper discusses some of the issues related to the toxic effects of lead on the skeleton and supports the supposition that this heavy metal may be an unrecognized and unappreciated agent in the etiology of diseases such as osteoporosis.

ISSN:1041-9918    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Fracture repair is a complex, specialized process whereby bone regenerates to restore pre-injury function to the skeleton. Despite successful healing in the majority of cases, a significant number of fractures require further treatment for delayed union or nonunion. As our knowledge of the molecular mechanisms that govern fracture repair continues to improve, new strategies for developing biologically based therapies will follow. This review examines the molecular aspects of adult skeletogenesis.

ISSN:1041-9918    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Nonunions, which occur in over 100,000 patients in the United States per year, are significant consequences in treating fractures. Ultrasound is a form of mechanical energy transmitted to bone as high frequency acoustic pressure waves. Previous trials have suggested that ultrasound significantly reduces the healing time of conservatively managed tibial shaft and distal radial fractures. Recent evidence suggests that ultrasound's utility may also be generalized to scaphoid fractures. However, a recent randomized trial suggests that ultrasound offers no additional benefit in those patients with tibial shaft fractures treated with reamed intramedullary nailing. Here, we present an overview of the recent clinical advances with ultrasound therapy and pulsed electromagnetic field therapy in augmenting fracture healing. We also conduct a meta-analysis of randomized trials to include this recent evidence.

ISSN:1041-9918    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Full thickness focal lesions of articular cartilage are particularly challenging for the clinician. Left untreated, these lesions invariably develop into osteoarthritis, damaging the surrounding cartilage and causing long-term pain and debilitation. We review the uses of isolated and gene-transformed cells derived from cartilage, perichondrium, periosteum, and bone marrow and seeded into polymeric scaffolds to resurface full thickness cartilage defects. Novel gene therapy methods are being developed at a rapid pace to introduce particular beneficial genes into the seeded cells. These gene-modified cells form the prototypic `factories' to locally deliver growth-and transcription-factors at the repair site to maintain the implanted cells in a chondrocytic phenotype and may affect repair in a regulated process akin to development.

ISSN:1041-9918    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Bone transplantation via autograft or allograft is an essential component of surgical management for a variety of skeletal defects. The nondegradable poly(methylmethacrylate) finds use as a bone graft alternative in certain limited clinical situations. There is an array of degradable, synthetic alternatives to these existing choices on the clinical use horizon. These alternatives include a variety of polymeric and ceramic composite materials that can provide immediate structural stability to the reconstructed region. In addition, these materials can deliver cells and growth factors to direct the bone regeneration process. This review discusses recent work in this rapidly evolving field of bone tissue engineering.

ISSN:1041-9918    

出版商:OVID    

年代:2000

数据来源: OVID