Severe Alterations of Bone Mass and Bone Structure after Allogeneic Stem Cell Transplantation: An Osteopathologic Analysis.

Prolonged survival after allogeneic SCT has led to an increased awareness of late complications in these patients. Loss of bone density after SCT has been reported in radiologic analyses (Ebeling 1999, Schulte 2000, Massenkeil 2001). We have studied bone mass and structure alterations in bone marrow biopsies after SCT.

Patients and Methods: 67 patients after allogeneic SCT were included in this analysis. Median age was 36 years (range 17–56), 35 male, 32 female. Diagnoses were: ALL 27 patients, AML 14, MDS 6, CML 20. 38 patients were in 1. CR or 1. cP, 29 were transplanted with advanced disease. 64 received standard high-dose conditioning and 3 were transplanted after reduced intensity conditioning. 42 received bone marrow and 25 mobilized peripheral blood as stem cell source.40 patients were transplanted from HLA-identical related and 27 from unrelated donors.

31 bone marrow biopsies underwent Micro-CT (Scanco, Zürich, CH) and were analysed after 3-D reconstruction. Usual parameters of trabecular structure were investigated.

Results: Median bone volume/tissue volume (BV/TV), which serves as a parameter of histopathologic bone mass was 13.7% before SCT (range 8.6–44.4%), well below 18%, which are considered the osteopathologic threshold for osteoporosis. At first follow-up 6–9 months after SCT, BV/TV had dropped to 10.1% (5.9–24.6%) and at 1–2 years after SCT BV/TV was still below the pre-SCT values at 12.2% (6.1–19.3%).

Number of trabecules (Tb.N.) dropped from 1.63/mm (range 0.93–2.32/mm) to 1.34 (1.01–5.61/mm) after 6–9 months and slightly increased to 1.54 (1.26–1.88/mm) after 1–2 years.

Trabecular thickness (Tb. Th.) fell from 0.20 mm before SCT (normal Tb. Th. 0.20–0.30 mm) (range 0.16–0.49 mm) to a minimum of 0.16 mm (0.14–0.25 mm).

As a consequence, intertrabecular space (Tb.Sp., normal appx. 0.60 mm) increased from 0.60 mm (0.36–1.11 mm) to 0.73 mm (0.23–1.04 mm) after SCT.

Discussion: Independently from underlying diagnosis trabecular parameters changed within the first 6 months after SCT, indicating early loss of bone mass and structure. Afterwards, they showed some tendency to normalization, however, none of the parameters went back to baseline values. Number of patients analysed over time was to small to find out causative clinical parameters like chronic GvHD. Radiologic bone density was available for these patients and showed synchronous variations over time.

Conclusions: Structural changes of trabecular bone develop early after allogeneic SCT and underscore the severeness of bone loss observed in these patients. Even after prolonged follow-up, structural changes and diminished bone mass persist and indicate a long-term cause of morbidity in these patients.