Bone
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Cancer progression and metastasis occur such that cells with acquired mutations enhancing growth and survival (or inhibiting cell death) increase in number, a concept that has been recognized as analogous to Darwinian evolution of species since Peter C. Nowell's description in 1976. Selective forces include those intrinsic to the host (including metastatic site) as well as those resulting from anti-cancer therapies. By examining the mutational status of multiple tumor sites within an individual patient some insight may be gained into those genetic variants that enhance site-specific metastasis. By comparing these data across multiple individuals, recurrent patterns may identify alterations that are fundamental to successful site-specific metastasis. ⋯ Mitochondrial genomic variation was greater in metastatic sites than in the primary tumor and bone metastases had statistically significantly greater numbers of somatic mutations than either the primary or the soft tissue metastases. The genome was not mutated randomly. At least one mutational "hot-spot" was identified at the individual base level (nucleotide position 10398 in bone metastases) indicating a pervasive selective pressure for bone metastatic cells that had acquired the 10398 mtDNA mutation. Two additional recurrent mutations (tRNA Arg and tRNA Thr) support the concept of bone site-specific "survival of the fittest" as revealed by variation in the mitochondrial genome and selective pressure exerted by the metastatic site.
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Deficient levels of 25-hydroxyvitamin D [25(OH)D] have been associated with increased fracture risk. Racial differences in fracture risk may be related to differences in bioavailable vitamin D due to single nucleotide polymorphism (SNP) variations in the vitamin D binding protein (DBP). ⋯ Deficient 25(OH)D levels are associated with higher incidence of hospitalized fractures. Marginal effects were seen in Whites for the DBP genotype associated with lower bioavailable vitamin D, but result inconclusive. Further investigation is needed to more directly evaluate the association between bioavailable vitamin D and fracture risk.
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Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed medications to treat depression and anxiety. SSRIs exert their effects by inhibiting the serotonin transporter and modulating extracellular serotonin levels, a neurotransmitter that has been shown to affect bone metabolism in animals. Studies in adults suggest a negative association between SSRI use and bone mineral density (BMD), greater rates of bone loss with SSRI use and increased risk of fractures. However, the results on bone mass have been inconsistent. Furthermore, there is a dearth of studies examining an association between SSRI use and bone mass in the pediatric and adolescent age group. ⋯ In this NHANES study, adolescents treated with SSRIs had lower DXA measurements of the total femur and lumbar spine compared to SSRI non-users. These findings support the need for future prospective studies to examine the effects of SSRI use on bone mass in adolescents.