Blood cell production and bone homeostasis are physically interlinked systems that exhibit active cross-talk. We examined how bone health is affected in patients with hematopoietic disorders due to abnormal proliferation of bone marrow cells. The electronic databases Medline, Embase, PubMed, BIOSIS Previews, Web of Science, and Cochrane were searched for studies presenting numerical values for trabecular bone volume or bone mineral density in control and patients with hematopoietic disorders. We identified 5 studies for beta-thalassemia, 6 for sickle cell anemia, 2 for polycythemia vera and essential thrombocythemia, 3 for chronic myelogenous leukemia, 6 for myelofibrosis, 5 for multiple myeloma, and 4 studies each for systemic mastocytosis, lymphocytic leukemia, and hemochromatosis. The effect of the disease state on bone density was significant and negative for beta-thalassemia (r = -2.00; 95% confidence interval [CI] -3.41, -0.58; p < 0.005), sickle cell anemia (-0.91; -1.36, -0.47; p < 0.00005), chronic myelogenous leukemia (-0.55; -0.88, -0.22; p < 0005), mastocytosis (-0.99; -1.16, -0.82; p < 0.00001), lymphoblastic leukemia (-0.69; -0.98, -0.40; p < 0.00001), multiple myeloma (-0.67; -0.99, -0.35; p < 0.00005), and hemochromatosis (-1.15; -1.64, -0.66; p < 0.00001). The changes were negative but not significant for polycythemia vera (-0.16; -0.38, 0.05; p = 0.069) and essential thrombocythemia (-0.33; -0.92, 0.26; p = 0.14). In myelofibrosis, disease state was associated with increased bone density (0.74; 0.12, 1.36; p < 0.05). Bone density change significantly and negatively correlated with the level of ferritin and bone marrow cellularity but not with hemoglobin or erythropoietin. Thus, independent of hematopoietic lineage, abnormal proliferation of bone marrow cells appears to be associated with bone loss. Iron metabolism may independently contribute to bone homeostasis. © 2016 American Society for Bone and Mineral Research.

Key pointsr Most missense long QT syndrome type 2 (LQTS2) mutations result in Kv11.1 channels that show reduced levels of membrane expression.r Pharmacological chaperones that rescue mutant channel expression could have therapeutic potential to reduce the risk of LQTS2-associated arrhythmias and sudden cardiac death, but only if the mutant Kv11.1 channels function normally (i.e. like WT channels) after membrane expression is restored.r Fewer than half of mutant channels exhibit relatively normal function after rescue by low temperature. The remaining rescued missense mutant Kv11.1 channels have perturbed gating and/or ion selectivity characteristics.r Co-expression of WT subunits with gating defective missense mutations ameliorates but does not eliminate the functional abnormalities observed for most mutant channels.r For patients with mutations that affect gating in addition to expression, it may be necessary to use a combination therapy to restore both normal function and normal expression of the channel protein. AbstractIn the heart, Kv11

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