Postmenopausal osteoporosis is the most common bone disease, associated with low bone mineral
density (BMD) and pathological fractures which lead to significant morbidity. It is defined
clinically by a BMD of 2.5 standard deviations or more below the young female adult mean (T-score
=−2.5). Osteoporosis was a huge global problem both socially and economically
– in the UK alone, in 2011 £6 million per day was spent on treatment and social care
of the 230,000 osteoporotic fracture patients – and therefore viable preventative and
therapeutic approaches are key to managing this problem within the aging population of today. One of
the main issues surrounding the potential of osteoporosis management is diagnosing patients at risk
before they develop a fracture. We discuss the current and future possibilities for identifying
susceptible patients, from fracture risk assessment to shape modeling and in relation to the high
heritability of osteoporosis now that a plethora of genes have been associated with low BMD and
osteoporotic fracture. This review highlights the current therapeutics in clinical use (including
bisphosphonates, anti-RANKL [receptor activator of NF-κB ligand],
intermittent low dose parathyroid hormone, and strontium ranelate) and some of those in development
(anti-sclerostin antibodies and cathepsin K inhibitors). By highlighting the intimate relationship
between the activities of bone forming (osteoblasts) and bone-resorbing (osteoclasts) cells, we
include an overview and comparison of the molecular mechanisms exploited in each therapy.
Very little is understood about genetic mechanisms underlying the onset of spring migration in latitudinal avian migrants. To gain insight into the genetic architecture of the hypothalamus and liver tissues of a long-distance migrant, we examined and compared the transcriptome profile of captive night-migratory black-headed buntings (Emberiza melanocephala) between photoperiod-induced winter non-migratory (WnM) and spring migratory (SM) life-history states under short and long days, respectively. High-throughput 454 pyrosequenced transcripts were mapped initially with reference to the genome of two phylogenetically close species, Taeniopygia guttata and Ficedula albicollis. The F. albicollis genome gave higher annotation results and was used for further analysis. A total of 216 (78 in hypothalamus; 138 in liver) genes were found to be expressed differentially between the WnM and SM life-history states. These genes were enriched for physiological pathways that might be involved in the regulation of seasonal migrations in birds. For example, genes for the ATP binding pathway in the hypothalamus were expressed at a significantly higher level in SM than in the WnM life-history state. Likewise, upregulated genes associated with the myelin sheath and focal adhesion were enriched in the hypothalamus, and those with cell-to-cell junction, intracellular protein transport, calcium ion transport and small GTPase-mediated signal transduction were enriched in the liver. Many of these genes are a part of physiological pathways potentially involved in the regulation of seasonal migration in birds. These results show molecular changes at the regulatory and metabolic levels associated with seasonal transitions in a long-distance migrant and provide the basis for future studies aimed at unravelling the genetic control of migration in birds.
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