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. 2024 Sep:186:117141.
doi: 10.1016/j.bone.2024.117141. Epub 2024 May 31.

Underlying systemic mastocytosis in patients with unexplained osteoporosis: score proposal

Ilaria Tanasi  1 , Lara Crosera  2 , Francesco Taus  3 , Giovanni Orsolini  4 , Giovanni Adami  5 , Francesco Olivieri  6 , Andrea Bernardelli  2 , Patrizia Bonadonna  6 , Francesca Nalin  6 , Stefania Sella  7 , Sandro Giannini  7 , Yihui Liu  8 , Francesco Mannelli  9 , Fiorenza Vanderwert  9 , Massimiliano Bonifacio  10 , Mauro Krampera  11 , Maurizio Rossini  4 , Jonathan J Lyons  8 , Roberta Zanotti  12
Affiliations

Underlying systemic mastocytosis in patients with unexplained osteoporosis: score proposal

Ilaria Tanasi et al. Bone. 2024 Sep.

Abstract

Background: A score to predict the association between unexplained osteoporosis and an underlying systemic Mastocytosis (SM) is lacking.

Objective: This study aimed at identifying criteria able to predict the diagnosis of SM without skin involvement and provide an indication for bone marrow (BM) assessment.

Methods: We included 139 adult patients with unexplained osteoporosis and suspected SM. After BM evaluation, 63 patients (45.3 %) were diagnosed with SM, while the remaining 76 patients (54.7 %) negative for clonal mast cell (MC) disorders, constituted our control group. Univariate and multivariate analysis identified three independent predictive factors: age (<54 years: +1 point, >64 years: -1 point), serum basal tryptase (sBT) levels >19 ng/mL (+2 points) and vertebral fractures (+2 points).

Results: These variables were used to build the OSTEO-score, able to predict the diagnosis of SM before BM assessment with a sensitivity of 73.5 % and a specificity of 67.1 %. Patients with a score < 3 had a lower probability of having SM compared to patients with a score ≥ 3 (28.5 % and 71.4 %, respectively, p < 0.0001). When sBT levels were corrected for the presence of hereditary alpha-tryptasemia (HαT) using the BST calculater (https://bst-calculater.niaid.nih.gov/) recently published [1,2], the sensitivity of ΗαT-adjusted OSTEO-score increased to 87.8 %, and the specificity reached 76.1 %. Also, the positive predictive value of a score ≥ 3 increased to 85.2 %.

Conclusions: Further studies are needed to validate these results and characterize the role of tryptase genotyping in patients with unexplained osteoporosis in reducing the risk of misdiagnosing patients with SM. Our proposed scoring model allows the identification of patients with the highest probability of having SM, avoiding unnecessary BM studies.

Keywords: Bone marrow mastocytosis; Hereditary alpha tryptasemia; Predictive score; Severe osteoporosis; Systemic mastocytosis.

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Conflict of interest statement

Declaration of competing interest All the authors have approved this manuscript and declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Figure 1.
Figure 1.
OSTEO-score proposed for patients with unexplained osteoporosis before a BM study.
Figure 2:
Figure 2:
a. Distribution of SM patients (n=63) and controls (n=76) according to our OSTEO-score; b. Distribution of 54 patients (SM patients, n=33; controls, n=21) according to OSTEO-score after correction of sBT levels in patients with HαT according to Valent et al. [26]
Figure 2:
Figure 2:
a. Distribution of SM patients (n=63) and controls (n=76) according to our OSTEO-score; b. Distribution of 54 patients (SM patients, n=33; controls, n=21) according to OSTEO-score after correction of sBT levels in patients with HαT according to Valent et al. [26]
Figure 3:
Figure 3:
HαT -adjusted OSTEO-score proposed for patients with unexplained osteoporosis before a BM study.
Figure 4:
Figure 4:
Distribution of SM patients (n=33) and controls (n=21) according to HαT-adjusted OSTEO-score, after correction of sBT levels in patients with HαT according to Chovanec et al. [1]
Figure 5.
Figure 5.
Proposed diagnostic pathway for patients with unexplained osteoporosis, without skin lesions, in suspicion of SM. Legend: HαT=hereditary alpha tryptasemia; PB= peripheral blood; BM= bone marrow; sBT= serum basal tryptase.
See this image and copyright information in PMC

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