Clinical Reviews in Bone and Mineral Metabolism最新文献

Paget's disease of bone (PDB) is the second most common metabolic bone disorder, after osteoporosis. It is characterised by focal areas of increased and disorganised bone turnover, coupled with increased bone formation. This disease usually appears in the late stages of life, being slightly more frequent in men than in women. It has been reported worldwide, but primarily affects individuals of British descent. Majority of PDB patients are asymptomatic, but clinical manifestations include pain, bone deformity and complications, like pathological fractures and deafness. The causes of the disease are poorly understood and it is considered as a complex trait, combining genetic predisposition with environmental factors. Linkage analysis identified SQSTM1, at chromosome 5q35, as directly related to the disease. A number of mutations in this gene have been reported, pP392L being the most common variant among different populations. Most of these variants affect the ubiquitin-associated (UBA) domain of the protein, which is involved in autophagy processes. Genome-wide association studies enlarged the number of loci associated with PDB, and further fine-mapping studies, combined with functional analysis, identified OPTN and RIN3 as causal genes for Paget's disease. A combination of risk alleles identified by genome-wide association studies led to the development of a score to predict disease severity, which could improve the management of the disease. Further studies need to be conducted to elucidate other important aspects of the trait, such as its focal nature and the epidemiological changes found in some populations. In this review, we summarize the clinical characteristics of the disease and the latest genetic advances to identify susceptibility genes. We also list current available treatments and prospective options.

The link between low bone mineral density (BMD) scores leading to greater fracture risk is well established in the literature; what is not fully understood is the impact of total knee replacements/revisions or arthroplasties on BMD levels. This literature review attempts to answer this question. Several different databases using specific key terms were searched, with additional papers retrieved via bibliographic review. Based on the available evidence, total knee replacements/revisions and arthroplasties lower BMD and thus increase fracture risk. This review also addresses the possible implications of this research and possible options to reduce this risk.

This review presents an overview of the characterization techniques available to experimentally evaluate bone quality, defined as the geometric and material factors that contribute to fracture resistance independently of areal bone mineral density (aBMD) assessed by dual energy x-ray absorptiometry. The methods available for characterization of the geometric, compositional, and mechanical properties of bone across multiple length scales are summarized, along with their outcomes and their advantages and disadvantages. Examples of how each technique is used are discussed, as well as practical concerns such as sample preparation and whether or not each testing method is destructive. Techniques that can be used in vivo and those that have been recently improved or developed are emphasized, including high resolution peripheral quantitative computed tomography to evaluate geometric properties and reference point indentation to evaluate material properties. Because no single method can completely characterize bone quality, we provide a framework for how multiple characterization methods can be used together to generate a more comprehensive analysis of bone quality to complement aBMD in fracture risk assessment.