A histomorphometric study of haematological disorders with respect to marrow fibrosis and osteosclerosis

Abstract

A retrospective investigation of 75 EDTA‐decalcified Jamshidi biopsies collected over a 2‐year period at Aarhus University Hospital was performed. The biopsies originated from 75 patients suffering from idiopathic myelofibrosis, other chronic myeloproliferative disorders, or other conditions with known associations with bone marrow fibrosis. The relative volumes of trabecular and woven bone, as well as haematopoietic and non‐haematopoietic tissue, were estimated histomorphometrically. The degree of fibrosis was estimated semiquantitatively. Finally, the thickness of trabecular osteons was estimated from the number of lamellae by counting. Patients with idiopathic myelofibrosis had statistically significantly more bone tissue than the other groups of patients. The osteosclerosis was primarily due to woven bone. Larger cancellous osteons also suggested a positive balance in bone remodelling. The amount of bone tissue showed furthermore a statistically significant increase through the groups of polycythaemia vera, essential thrombocythaemia, chronic myelogenous leukaemia and idiopathic myelofibrosis. Parallel to the increase in the amount of bone, an increase in the degree of marrow fibrosis was detected. The positive correlation between the amount of bone and the degree of marrow fibrosis was statistically highly significant (p=0.0008).

Constitutive mobilization of CD34+ cells into the peripheral blood in idiopathic myelofibrosis may be due to the action of a number of proteases

“…29 The aberrant cellular trafficking in IM has been previously attributed to the disruption of the BM microenvironment, which occurs as a result of reactive BM fibrosis and osteosclerosis. 37 This explanation seems unlikely, however, since allogenic stem cell transplantation of peripheral blood grafts for patients with IM is not characterized by delayed engraftment or a high rate of graft failure. [38][39][40][41] Surprisingly, the rate of graft failure has been reported to be higher following autologous stem cell transplantation than allogenic stem cell transplantation, [38][39][40][41] suggesting that HSC/HPC homing and engraftment are not adversely affected by the BM microenvironment in IM.…”

Bone morbidity in chronic myeloproliferative neoplasms

“…Histomorphometric measurements in a cohort of 75 MPN patients have shown that MF patients have significantly more bone tissue compared with other MPN-type patients, and that there is a positive correlation between the amount of bone and the degree of fibrosis [25]. Bone appositions are due to a thickening of existing trabeculae and not gain of new trabeculae [26].…”

Megakaryocyte–Bone Marrow Stromal Cell Aggregates Demonstrate Increased Colony Formation and Alkaline Phosphatase Expressionin Vitro

“…It is now generally accepted that megakaryocytes play a causal role in myelofibrosis, 31,32 and this in turn is associated with osteosclerosis. 33,34 In addition, increased numbers of megakaryocytes were observed in postmenopausal women receiving high-dose estradiol therapy, 35 mice treated with high-dose estradiol, 36 and rats treated with high-dose 1,25-(OH) 2 vitamin D 3 . 36a Although megakaryocytes produce a number of growth factors such as platelet-derived growth factor (PDGF) or transforming growth factor ␤ (TGF-␤), known to modulate the growth of BMSCs, 26,27,37 it is unlikely that these play a role in the activity described here.…”