Serum levels of bone cytokines are increased in indolent systemic mastocytosis associated with osteopenia or osteoporosis Anja Rabenhorst, PhD, Bastian.

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Serum levels of bone cytokines are increased in indolent systemic mastocytosis associated with osteopenia or osteoporosis Anja Rabenhorst, PhD, Bastian Christopeit, MD, Silke Leja, MTA, Alexander Gerbaulet, PhD, Svea Kleiner, MSc, Anja Förster, MSc, Ulrike Raap, MD, Claudia Wickenhauser, MD, Karin Hartmann, MD Journal of Allergy and Clinical Immunology Volume 132, Issue 5, Pages 1234-1237.e7 (November 2013) DOI: 10.1016/j.jaci.2013.06.019 Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 A-B, Overlay of the normal BMD distribution in controls (black dotted line) against the observed BMD in patients with SM (patient group 1; red line) at lumbar spine (Fig 1, A) and femoral neck (Fig 1, B). Bars show the number of patients per T score. C-H, Tryptase (Fig 1, C), IL-6 (Fig 1, D), RANKL (Fig 1, E), OPG (Fig 1, F), Dkk-1 (Fig 1, G), and SOST (Fig 1, H) serum levels in patients with ISM (patient group 2) and controls. Data are presented as box plots (minimum to maximum) with medians (left) and scatter dot plots with means (right). I-J, Expression of tryptase, RANKL, and OPG in the BM of patients with SM analyzed by immunohistochemistry (Fig 1, I) and immunofluorescence (Fig 1, J). K, RANKL, OPG, and SOST levels in supernatants of cultured MCs (HMC1.1 and HMC1.2) compared with osteoblast cell lines (SaOs, MG63). Journal of Allergy and Clinical Immunology 2013 132, 1234-1237.e7DOI: (10.1016/j.jaci.2013.06.019) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Mechanism of bone destruction in mastocytosis-associated osteoporosis. MC-derived bone cytokines, including IL-6, RANKL, OPG, Dkk-1, and SOST, could directly affect functions of osteoblasts and osteoclasts, shifting the complex balance of bone turnover toward increased bone resorption and decreased bone formation. Journal of Allergy and Clinical Immunology 2013 132, 1234-1237.e7DOI: (10.1016/j.jaci.2013.06.019) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 A-B, BMD of lumbar spine (Fig E1, A) and femoral neck (Fig E1, B) are comparable in female (n = 36) and male (n = 20) patients with SM (patient group 1; n = 56). C-D, BMD of lumbar spine (Fig E1, C) and femoral neck (Fig E1, D) are comparable in patients with SM younger than 50 years (n = 31) and older than 50 years (n = 25). E-F, BMD of lumbar spine (Fig E1, E) and femoral neck (Fig E1, F) in different categories of SM. Data are presented as box plots (minimum to maximum) with medians (left) and scatter dot plots with means (right). Colors illustrate scoring for bone disease (blue, osteoporosis; green, osteopenia; yellow, normal; beige, osteosclerosis). AHNMD, Associated hematologic non-MC lineage disease; SSM, smoldering SM. Journal of Allergy and Clinical Immunology 2013 132, 1234-1237.e7DOI: (10.1016/j.jaci.2013.06.019) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 A-B, BMD of lumbar spine (Fig E2, A) and femoral neck (Fig E2, B) in patient group 2 (ISM subgroup; n = 21). Data are presented as box plots (minimum to maximum) with medians (left) and scatter dot plots with means (right). Colors illustrate scoring for bone disease (blue, osteoporosis; green, osteopenia; yellow, normal; beige, osteosclerosis). C, Calcium, PTH, and vitamin D in patient group 2 (ISM subgroup; n = 21) and healthy controls (control; n = 10). Data are presented as box plots (minimum to maximum) with medians (left) and scatter dot plots with means (right). Journal of Allergy and Clinical Immunology 2013 132, 1234-1237.e7DOI: (10.1016/j.jaci.2013.06.019) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions