Skip to main content
Top
Published in: Osteoporosis International 8/2013

01-08-2013 | Original Article

Increased osteoblast and osteoclast indices in individuals with systemic mastocytosis

Authors: S. Seitz, F. Barvencik, T. Koehne, M. Priemel, P. Pogoda, J. Semler, H. Minne, M. Pfeiffer, J. Zustin, K. Püschel, C. Eulenburg, T. Schinke, M. Amling

Published in: Osteoporosis International | Issue 8/2013

Login to get access

Abstract

Summary

Indolent systemic mastocytosis (ISM) can trigger bone loss. However, the clinical relevance of different mast cell infiltration patterns for bone remains to be clarified. Here, we report increased bone turnover in individuals with ISM, and its extent is rather related to the type of mast cell distribution within the bone marrow than to the presence or absence of cutaneous manifestations.

Introduction

It is well established that ISM can trigger osteopenia or osteoporosis. However, neither the clinical relevance of the infiltration pattern of mast cells within the bone marrow nor the impact of the presence or absence of cutaneous mast cell infiltration has been elucidated.

Methods

We retrospectively analysed 300 cases with histologically proven ISM of the bone marrow and performed quantitative histomorphometry for a subgroup of 159 patients that did not receive any treatment before the biopsies were taken. Most importantly, since 66 % of the patients displayed ISM without the characteristic skin lesions, we were able to compare ISM with or without cutaneous manifestation.

Results

We found that both forms of ISM were not only characterized by a decreased trabecular bone mass but also by an increased number of osteoclasts and osteoblasts. Interestingly, when we analysed these data in relation to mast cell distribution, we found that the bone cell numbers in cases with mast cell granulomas were significantly increased compared to cases with diffuse mast cell distribution. Moreover, evidence of increased bone turnover was also found in 16 patients displaying osteosclerosis.

Conclusion

Based on the largest cohort of bone biopsies from patients with ISM analysed so far, we could demonstrate high bone turnover, more specifically increased osteoblast and osteoclast numbers and surface indices, as a cause of the skeletal changes. Moreover, the severity of the bone disease is presumably rather dependent on the amount of mast cells and their distribution within the bone marrow irrespective of the presence or absence of cutaneous involvement.
Appendix
Available only for authorised users
Literature
1.
go back to reference Valent P, Horny HP, Escribano L et al (2001) Diagnostic criteria and classification of mastocytosis: a consensus proposal. Leuk Res 25:603–625PubMedCrossRef Valent P, Horny HP, Escribano L et al (2001) Diagnostic criteria and classification of mastocytosis: a consensus proposal. Leuk Res 25:603–625PubMedCrossRef
3.
4.
go back to reference Horny HP, Akin C, Metcalfe DD (2008) Mastocytosis (mast cell disease). In: Swerdlow S, Campo E, Harris N, Jaffe E, Pileri S, Stein H (eds) World health organization (WHO) classification of tumours pathology & genetics tumours of haematopoietic an lymphoid tissues. IARC, Lyon, pp 54–63 Horny HP, Akin C, Metcalfe DD (2008) Mastocytosis (mast cell disease). In: Swerdlow S, Campo E, Harris N, Jaffe E, Pileri S, Stein H (eds) World health organization (WHO) classification of tumours pathology & genetics tumours of haematopoietic an lymphoid tissues. IARC, Lyon, pp 54–63
5.
go back to reference Barete S, Assous N, de Gennes C et al (2010) Systemic mastocytosis and bone involvement in a cohort of 75 patients. Ann Rheum Dis 69:1838–1841PubMedCrossRef Barete S, Assous N, de Gennes C et al (2010) Systemic mastocytosis and bone involvement in a cohort of 75 patients. Ann Rheum Dis 69:1838–1841PubMedCrossRef
6.
go back to reference van der Veer E, van der Goot W, de Monchy JG, Kluin-Nelemans HC, van Doormaal JJ (2012) High prevalence of fractures and osteoporosis in patients with indolent systemic mastocytosis. Allergy 67:431–438PubMedCrossRef van der Veer E, van der Goot W, de Monchy JG, Kluin-Nelemans HC, van Doormaal JJ (2012) High prevalence of fractures and osteoporosis in patients with indolent systemic mastocytosis. Allergy 67:431–438PubMedCrossRef
7.
go back to reference Rossini M, Zanotti R, Bonadonna P et al (2011) Bone mineral density, bone turnover markers and fractures in patients with indolent systemic mastocytosis. Bone 49:880–885PubMedCrossRef Rossini M, Zanotti R, Bonadonna P et al (2011) Bone mineral density, bone turnover markers and fractures in patients with indolent systemic mastocytosis. Bone 49:880–885PubMedCrossRef
8.
go back to reference Delling G, Ritzel H, Werner M (2001) Histological characteristics and prevalence of secondary osteoporosis in systemic mastocytosis. Pathologe 22:132–140PubMedCrossRef Delling G, Ritzel H, Werner M (2001) Histological characteristics and prevalence of secondary osteoporosis in systemic mastocytosis. Pathologe 22:132–140PubMedCrossRef
9.
go back to reference McKenna MJ, Frame B (1985) The mast cell and bone. Clin Orthop Relat Res 200:226–233PubMed McKenna MJ, Frame B (1985) The mast cell and bone. Clin Orthop Relat Res 200:226–233PubMed
10.
go back to reference Kanzaki S, Takahashi T, Kanno T, Ariyoshi W, Shinmyouzu K, Tujisawa T, Nishihara T (2008) Heparin inhibits BMP-2 osteogenic bioactivity by binding to both BMP-2 and BMP receptor. J Cell Physiol 216:844–850PubMedCrossRef Kanzaki S, Takahashi T, Kanno T, Ariyoshi W, Shinmyouzu K, Tujisawa T, Nishihara T (2008) Heparin inhibits BMP-2 osteogenic bioactivity by binding to both BMP-2 and BMP receptor. J Cell Physiol 216:844–850PubMedCrossRef
11.
go back to reference Biosse-Duplan M, Baroukh B, Dy M, de Vernejoul MC, Saffar JL (2009) Histamine promotes osteoclastogenesis through the differential expression of histamine receptors on osteoclasts and osteoblasts. Am J Pathol 174:1426–1434PubMedCrossRef Biosse-Duplan M, Baroukh B, Dy M, de Vernejoul MC, Saffar JL (2009) Histamine promotes osteoclastogenesis through the differential expression of histamine receptors on osteoclasts and osteoblasts. Am J Pathol 174:1426–1434PubMedCrossRef
12.
go back to reference Brockow K, Akin C, Huber M, Metcalfe DD (2005) IL-6 levels predict disease variant and extent of organ involvement in patients with mastocytosis. Clin Immunol 115:216–223PubMedCrossRef Brockow K, Akin C, Huber M, Metcalfe DD (2005) IL-6 levels predict disease variant and extent of organ involvement in patients with mastocytosis. Clin Immunol 115:216–223PubMedCrossRef
13.
go back to reference Fallon MD, Whyte MP, Teitelbaum SL (1981) Systemic mastocytosis associated with generalized osteopenia. Histopathological characterization of the skeletal lesion using undecalcified bone from two patients. Hum Pathol 12:813–820PubMedCrossRef Fallon MD, Whyte MP, Teitelbaum SL (1981) Systemic mastocytosis associated with generalized osteopenia. Histopathological characterization of the skeletal lesion using undecalcified bone from two patients. Hum Pathol 12:813–820PubMedCrossRef
14.
go back to reference de Gennes C, Kuntz D, de Vernejoul MC (1992) Bone mastocytosis. A report of nine cases with a bone histomorphometric study. Clin Orthop Relat Res 279:281–291PubMed de Gennes C, Kuntz D, de Vernejoul MC (1992) Bone mastocytosis. A report of nine cases with a bone histomorphometric study. Clin Orthop Relat Res 279:281–291PubMed
15.
go back to reference Chines A, Pacifici R, Avioli LA, Korenblat PE, Teitelbaum SL (1993) Systemic mastocytosis and osteoporosis. Osteoporos Int 3(Suppl 1):147–149PubMedCrossRef Chines A, Pacifici R, Avioli LA, Korenblat PE, Teitelbaum SL (1993) Systemic mastocytosis and osteoporosis. Osteoporos Int 3(Suppl 1):147–149PubMedCrossRef
16.
go back to reference Chines A, Pacifici R, Avioli LV, Teitelbaum SL, Korenblat PE (1991) Systemic mastocytosis presenting as osteoporosis: a clinical and histomorphometric study. J Clin Endocrinol Metab 72:140–144PubMedCrossRef Chines A, Pacifici R, Avioli LV, Teitelbaum SL, Korenblat PE (1991) Systemic mastocytosis presenting as osteoporosis: a clinical and histomorphometric study. J Clin Endocrinol Metab 72:140–144PubMedCrossRef
17.
18.
go back to reference Zanotti R, Bonadonna P, Bonifacio M, Artuso A, Schena D, Rossini M, Perbellini O, Colarossi S, Chilosi M, Pizzolo G (2011) Isolated bone marrow mastocytosis: an underestimated subvariant of indolent systemic mastocytosis. Haematologica 96:482–484PubMedCrossRef Zanotti R, Bonadonna P, Bonifacio M, Artuso A, Schena D, Rossini M, Perbellini O, Colarossi S, Chilosi M, Pizzolo G (2011) Isolated bone marrow mastocytosis: an underestimated subvariant of indolent systemic mastocytosis. Haematologica 96:482–484PubMedCrossRef
19.
go back to reference Alvarez-Twose I, Gonzalez de Olano D, Sanchez-Munoz L et al (2010) Clinical, biological, and molecular characteristics of clonal mast cell disorders presenting with systemic mast cell activation symptoms. J Allergy Clin Immunol 125:1269–1278PubMedCrossRef Alvarez-Twose I, Gonzalez de Olano D, Sanchez-Munoz L et al (2010) Clinical, biological, and molecular characteristics of clonal mast cell disorders presenting with systemic mast cell activation symptoms. J Allergy Clin Immunol 125:1269–1278PubMedCrossRef
20.
go back to reference Turner RT, Iwaniec UT, Marley K, Sibonga JD (2010) The role of mast cells in parathyroid bone disease. J Bone Miner Res 25:1637–1649PubMedCrossRef Turner RT, Iwaniec UT, Marley K, Sibonga JD (2010) The role of mast cells in parathyroid bone disease. J Bone Miner Res 25:1637–1649PubMedCrossRef
21.
go back to reference Sanchez-Munoz L, Alvarez-Twose I, Garcia-Montero AC et al (2011) Evaluation of the WHO criteria for the classification of patients with mastocytosis. Mod Pathol 24:1157–1168PubMedCrossRef Sanchez-Munoz L, Alvarez-Twose I, Garcia-Montero AC et al (2011) Evaluation of the WHO criteria for the classification of patients with mastocytosis. Mod Pathol 24:1157–1168PubMedCrossRef
22.
go back to reference Cordell JL, Falini B, Erber WN, Ghosh AK, Abdulaziz Z, MacDonald S, Pulford KA, Stein H, Mason DY (1984) Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem 32:219–229PubMedCrossRef Cordell JL, Falini B, Erber WN, Ghosh AK, Abdulaziz Z, MacDonald S, Pulford KA, Stein H, Mason DY (1984) Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem 32:219–229PubMedCrossRef
23.
go back to reference Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, Ott SM, Recker RR (1987) Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR histomorphometry nomenclature committee. J Bone Miner Res 2:595–610PubMedCrossRef Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, Ott SM, Recker RR (1987) Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR histomorphometry nomenclature committee. J Bone Miner Res 2:595–610PubMedCrossRef
24.
go back to reference Seitz S, Koehne T, Ries C, et al. (2013) Impaired bone mineralization accompanied by low vitamin D and secondary hyperparathyroidism in patients with femoral neck fracture. Osteoporos Int 24:641–649 Seitz S, Koehne T, Ries C, et al. (2013) Impaired bone mineralization accompanied by low vitamin D and secondary hyperparathyroidism in patients with femoral neck fracture. Osteoporos Int 24:641–649
25.
go back to reference Dieckmann M, Beil FT, Mueller B et al (2013) Human apolipoprotein E isoforms differentially affect bone mass and turnover in vivo. J Bone Miner Res 28:236–245PubMedCrossRef Dieckmann M, Beil FT, Mueller B et al (2013) Human apolipoprotein E isoforms differentially affect bone mass and turnover in vivo. J Bone Miner Res 28:236–245PubMedCrossRef
26.
go back to reference Koehne T, Marshall RP, Jeschke A, Kahl-Nieke B, Schinke T, Amling M (2013) Osteopetrosis, osteopetrorickets and hypophosphatemic rickets differentially affect dentin and enamel mineralization. Bone 53:25–33PubMedCrossRef Koehne T, Marshall RP, Jeschke A, Kahl-Nieke B, Schinke T, Amling M (2013) Osteopetrosis, osteopetrorickets and hypophosphatemic rickets differentially affect dentin and enamel mineralization. Bone 53:25–33PubMedCrossRef
27.
go back to reference Roschger P, Fratzl P, Klaushofer K, Rodan G (1997) Mineralization of cancellous bone after alendronate and sodium fluoride treatment: a quantitative backscattered electron imaging study on minipig ribs. Bone 20:393–397PubMedCrossRef Roschger P, Fratzl P, Klaushofer K, Rodan G (1997) Mineralization of cancellous bone after alendronate and sodium fluoride treatment: a quantitative backscattered electron imaging study on minipig ribs. Bone 20:393–397PubMedCrossRef
28.
go back to reference Roschger P, Paschalis EP, Fratzl P, Klaushofer K (2008) Bone mineralization density distribution in health and disease. Bone 42:456–466PubMedCrossRef Roschger P, Paschalis EP, Fratzl P, Klaushofer K (2008) Bone mineralization density distribution in health and disease. Bone 42:456–466PubMedCrossRef
29.
go back to reference Ruffoni D, Fratzl P, Roschger P, Phipps R, Klaushofer K, Weinkamer R (2008) Effect of temporal changes in bone turnover on the bone mineralization density distribution: a computer simulation study. J Bone Miner Res 23:1905–1914PubMedCrossRef Ruffoni D, Fratzl P, Roschger P, Phipps R, Klaushofer K, Weinkamer R (2008) Effect of temporal changes in bone turnover on the bone mineralization density distribution: a computer simulation study. J Bone Miner Res 23:1905–1914PubMedCrossRef
30.
go back to reference Pardanani A, Lim KH, Lasho TL, Finke CM, McClure RF, Li CY, Tefferi A (2010) WHO subvariants of indolent mastocytosis: clinical details and prognostic evaluation in 159 consecutive adults. Blood 115:150–151PubMedCrossRef Pardanani A, Lim KH, Lasho TL, Finke CM, McClure RF, Li CY, Tefferi A (2010) WHO subvariants of indolent mastocytosis: clinical details and prognostic evaluation in 159 consecutive adults. Blood 115:150–151PubMedCrossRef
31.
go back to reference Escribano L, Alvarez-Twose I, Sanchez-Munoz L et al (2009) Prognosis in adult indolent systemic mastocytosis: a long-term study of the spanish network on mastocytosis in a series of 145 patients. J Allergy Clin Immunol 124:514–521PubMedCrossRef Escribano L, Alvarez-Twose I, Sanchez-Munoz L et al (2009) Prognosis in adult indolent systemic mastocytosis: a long-term study of the spanish network on mastocytosis in a series of 145 patients. J Allergy Clin Immunol 124:514–521PubMedCrossRef
32.
go back to reference Krokowski M, Sotlar K, Krauth MT, Fodinger M, Valent P, Horny HP (2005) Delineation of patterns of bone marrow mast cell infiltration in systemic mastocytosis: value of CD25, correlation with subvariants of the disease, and separation from mast cell hyperplasia. Am J Clin Pathol 124:560–568PubMedCrossRef Krokowski M, Sotlar K, Krauth MT, Fodinger M, Valent P, Horny HP (2005) Delineation of patterns of bone marrow mast cell infiltration in systemic mastocytosis: value of CD25, correlation with subvariants of the disease, and separation from mast cell hyperplasia. Am J Clin Pathol 124:560–568PubMedCrossRef
33.
go back to reference Horny HP, Kaiserling E (1988) Lymphoid cells and tissue mast cells of bone marrow lesions in systemic mastocytosis: a histological and immunohistological study. Br J Haematol 69:449–455PubMedCrossRef Horny HP, Kaiserling E (1988) Lymphoid cells and tissue mast cells of bone marrow lesions in systemic mastocytosis: a histological and immunohistological study. Br J Haematol 69:449–455PubMedCrossRef
34.
go back to reference Horny HP, Menke DM, Kaiserling E (1996) Neoplastic human tissue mast cells express the adhesion molecule CD44/HCAM. Virchows Arch 429:91–94PubMed Horny HP, Menke DM, Kaiserling E (1996) Neoplastic human tissue mast cells express the adhesion molecule CD44/HCAM. Virchows Arch 429:91–94PubMed
35.
go back to reference Thomsen JS, Ebbesen EN, Mosekilde L (2002) Static histomorphometry of human iliac crest and vertebral trabecular bone: a comparative study. Bone 30:267–274PubMedCrossRef Thomsen JS, Ebbesen EN, Mosekilde L (2002) Static histomorphometry of human iliac crest and vertebral trabecular bone: a comparative study. Bone 30:267–274PubMedCrossRef
36.
go back to reference Legrand E, Chappard D, Pascaretti C, Duquenne M, Krebs S, Rohmer V, Basle MF, Audran M (2000) Trabecular bone microarchitecture, bone mineral density, and vertebral fractures in male osteoporosis. J Bone Miner Res 15:13–19PubMedCrossRef Legrand E, Chappard D, Pascaretti C, Duquenne M, Krebs S, Rohmer V, Basle MF, Audran M (2000) Trabecular bone microarchitecture, bone mineral density, and vertebral fractures in male osteoporosis. J Bone Miner Res 15:13–19PubMedCrossRef
Metadata
Title
Increased osteoblast and osteoclast indices in individuals with systemic mastocytosis
Authors
S. Seitz
F. Barvencik
T. Koehne
M. Priemel
P. Pogoda
J. Semler
H. Minne
M. Pfeiffer
J. Zustin
K. Püschel
C. Eulenburg
T. Schinke
M. Amling
Publication date
01-08-2013
Publisher
Springer London
Published in
Osteoporosis International / Issue 8/2013
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-013-2305-x

Other articles of this Issue 8/2013

Osteoporosis International 8/2013 Go to the issue