Effect of different forms of MPN on human bone
| Reference . | Study purpose . | Pathology type . | Patients, n . | Finding . | Method . |
|---|---|---|---|---|---|
| Burkhardt et al, 198238 | Assess bone biopsy specimens in hematological disorders. | PV | 232 | Cohorts pooled for analyses. Attenuation of the cancellous trabeculae in PV and ET. Formation of irregular spicules of woven bone and progressive thickening of the trabeculae in osteomyelofibrosis. Lytic osseous lesions in association with focal accumulations of megakaryoblasts and MKs in CML. | Biopsy of the anterior or posterior iliac crests. Histology |
| ET (mentioned as MM) | 52 | ||||
| MF (fibrosis secondary to PV, CML) | 100 | ||||
| Osteomyelofibrosis (marrow fibrosis with trabecular thickening) | 84 | ||||
| CML | 143 | ||||
| Controls | 158 | ||||
| Coindre et al, 198439 | Analyze sclerotic bone from 9 patients with IMF with histomorphometry. | IMF (PMF) | 9 (6M; 3F) | Trabecular bone volume was higher in patients with IMF, compared with controls, and generally exceeded twice normal values. Female patients had higher trabecular volume than male patients. | Iliac bone biopsy. Histodynamic analysis on undecalcified bone. |
| Controls | 18 | ||||
| Thiele et al, 198940 | Elucidate osseous remodeling by assessment of trabecular bone area and number of OCs. | CML | 65 | Cohorts were pooled for analysis. No significant differences in the total area of trabecular bone and OC counts in CML, ET, and PV and initial stages of PMF. In advanced stages of PMF, significant increase in total bone area is associated with a high count for all osteoclastic elements and OBs. | Biopsy of posterior iliac crest. Histomorphometry |
| ET | 25 | ||||
| PV | 25 | ||||
| AMM (PMF) | 50 | ||||
| Control | 20 (9M; 11F) | ||||
| Poulsen et al, 199841 | Investigate degree of osteosclerosis and BM fibrosis in hematopoietic malignancies. No controls; only patients. Comparison was made between the different MPNs. | IMF (PMF) | 20 (10M; 10F) | Cohorts were pooled for analyses. IMF showed greater BM fibrosis and total bone volume compared with all other MPNs Fibrosis and osteosclerosis decreased gradually through IMF, CML, ET and PV. Both the amount of woven bone and the size of osteons positively correlated with the degree of fibrosis. | Jamshidi biopsies for histomorphometry. |
| CML | 10 (3M; 7F) | ||||
| ET | 10 (3M; 7F) | ||||
| PV | 5 (2M; 3F) | ||||
| Non-IMF | 25 (8M; 17F) | ||||
| CMPD-NOS | 2 (1M; 1F) | ||||
| Diamond et al, 200242 | Analyze 4 males with IMF | IMF (PMF) | 4M | Significant increases in osteoid thickness, trabecular thickness and cancellous bone volume. Evidence of high bone turnover. | Iliac crest bone biopsy for histomorphometry Serum biochemistry Markers of bone turnover Lumbar spine and femoral neck DXA Lumbar spine QCT |
| Controls (based on control values from a previous study119) | 113M | ||||
| Mellibovsky et al, 200443 | Determine bone remodeling alterations in IMF. | IMF (PMF) | 9 (5M; 4F) | Cohorts were pooled for analyses of the bone histomorphometric parameters. Patients with IMF showed significantly higher bone volume (BV/TV); OB surface (Ob.S./BS); OC surface (Os.S/BS); OC number (n, OC/TA); mineralizing surface (MS/BS); and eroded surface (ES/BS). | Transiliac bone biopsies Static and dynamic histomorphometry |
| Controls | 40 (22M; 18F) | ||||
| Schmidt et al, 200744 | Characterize cellular and tissular changes in bone from patients with MMM. | MMM (same as PMF). Controls were age-matched from the French population with data available.120,121 | 13 (8M; 5F) | No differences between M and F Increased thickness of bone units in some patients. Bone formation rate increased in 7 patients. Tendency for decrease of OC number Eroded surfaces increased in 10 patients. | Transiliac bone biopsies Histomorphometry Micro-CT |
| Fitter et al, 2008118 | Examine the effect of long-term imatinib or α-interferon therapy on bone of patients with CML. | CML | 29 (20M; 9F) | No differences between M and F. Before treatment: Trabecular bone volume was within the normal range in 15 patients, below normal in 10 patients, and exceeded the normal range in 4 patients (based on control values from a previous study122). | Posterior superior iliac spine trephine biopsies Histomorphometry |
| Teman et al, 201045 | Test the utility of digital imaging as an objective quantification method for both BM fibrosis and osteosclerosis. | PMF | 34 (19M; 15F) | Cohorts were pooled for analyses. All categories of MPN, except newly diagnosed CML, had significantly higher trabecular volume compared with controls. Trabecular volume was strikingly higher in PMF than in ET and PV. PMF had higher trabecular volume than MF that was secondary to other MPNs. There was no statistically significant relationship between JAK2 status and trabecular volume. | Posterior superior iliac spine trephine biopsies. Histomorphologic assessments of slides stained with hematoxylin and eosin and digitally scanned with a ScanScope XT system. |
| ET | 20 (9M; 11F) | ||||
| Post-ET MF | 14 (6M; 8F) | ||||
| PV | 14 (6M; 8F) | ||||
| Post-PV MF | 7 (3M; 4F) | ||||
| CML | 10 (6M; 4F) | ||||
| MPN-U (unclassifiable) | 22 (12M; 10F) | ||||
| Controls | 69 (41M; 28F) | ||||
| Farmer et al, 201546 | Assess bone geometry, bone mineral density, and microarchitecture in patients with MF. | MF (either primary MF or secondary to other MPN) | 18 (9M; 9F) | Cohorts were pooled for analyses. No significant differences between MF patients and controls regarding bone mineral density, geometry, and microarchitecture, despite manifestations of osteosclerosis observed in bone marrow biopsies of the patients. Bone stiffness and bone strength were similar between patients with MF and controls. | Lumbar spine and nondominant total hip region DXA. Nondominant distal radius and distal tibia HR-QCT. Measurements of biochemical markers for assessment of bone turnover. |
| Controls | 18 (9M; 9F) |
| Reference . | Study purpose . | Pathology type . | Patients, n . | Finding . | Method . |
|---|---|---|---|---|---|
| Burkhardt et al, 198238 | Assess bone biopsy specimens in hematological disorders. | PV | 232 | Cohorts pooled for analyses. Attenuation of the cancellous trabeculae in PV and ET. Formation of irregular spicules of woven bone and progressive thickening of the trabeculae in osteomyelofibrosis. Lytic osseous lesions in association with focal accumulations of megakaryoblasts and MKs in CML. | Biopsy of the anterior or posterior iliac crests. Histology |
| ET (mentioned as MM) | 52 | ||||
| MF (fibrosis secondary to PV, CML) | 100 | ||||
| Osteomyelofibrosis (marrow fibrosis with trabecular thickening) | 84 | ||||
| CML | 143 | ||||
| Controls | 158 | ||||
| Coindre et al, 198439 | Analyze sclerotic bone from 9 patients with IMF with histomorphometry. | IMF (PMF) | 9 (6M; 3F) | Trabecular bone volume was higher in patients with IMF, compared with controls, and generally exceeded twice normal values. Female patients had higher trabecular volume than male patients. | Iliac bone biopsy. Histodynamic analysis on undecalcified bone. |
| Controls | 18 | ||||
| Thiele et al, 198940 | Elucidate osseous remodeling by assessment of trabecular bone area and number of OCs. | CML | 65 | Cohorts were pooled for analysis. No significant differences in the total area of trabecular bone and OC counts in CML, ET, and PV and initial stages of PMF. In advanced stages of PMF, significant increase in total bone area is associated with a high count for all osteoclastic elements and OBs. | Biopsy of posterior iliac crest. Histomorphometry |
| ET | 25 | ||||
| PV | 25 | ||||
| AMM (PMF) | 50 | ||||
| Control | 20 (9M; 11F) | ||||
| Poulsen et al, 199841 | Investigate degree of osteosclerosis and BM fibrosis in hematopoietic malignancies. No controls; only patients. Comparison was made between the different MPNs. | IMF (PMF) | 20 (10M; 10F) | Cohorts were pooled for analyses. IMF showed greater BM fibrosis and total bone volume compared with all other MPNs Fibrosis and osteosclerosis decreased gradually through IMF, CML, ET and PV. Both the amount of woven bone and the size of osteons positively correlated with the degree of fibrosis. | Jamshidi biopsies for histomorphometry. |
| CML | 10 (3M; 7F) | ||||
| ET | 10 (3M; 7F) | ||||
| PV | 5 (2M; 3F) | ||||
| Non-IMF | 25 (8M; 17F) | ||||
| CMPD-NOS | 2 (1M; 1F) | ||||
| Diamond et al, 200242 | Analyze 4 males with IMF | IMF (PMF) | 4M | Significant increases in osteoid thickness, trabecular thickness and cancellous bone volume. Evidence of high bone turnover. | Iliac crest bone biopsy for histomorphometry Serum biochemistry Markers of bone turnover Lumbar spine and femoral neck DXA Lumbar spine QCT |
| Controls (based on control values from a previous study119) | 113M | ||||
| Mellibovsky et al, 200443 | Determine bone remodeling alterations in IMF. | IMF (PMF) | 9 (5M; 4F) | Cohorts were pooled for analyses of the bone histomorphometric parameters. Patients with IMF showed significantly higher bone volume (BV/TV); OB surface (Ob.S./BS); OC surface (Os.S/BS); OC number (n, OC/TA); mineralizing surface (MS/BS); and eroded surface (ES/BS). | Transiliac bone biopsies Static and dynamic histomorphometry |
| Controls | 40 (22M; 18F) | ||||
| Schmidt et al, 200744 | Characterize cellular and tissular changes in bone from patients with MMM. | MMM (same as PMF). Controls were age-matched from the French population with data available.120,121 | 13 (8M; 5F) | No differences between M and F Increased thickness of bone units in some patients. Bone formation rate increased in 7 patients. Tendency for decrease of OC number Eroded surfaces increased in 10 patients. | Transiliac bone biopsies Histomorphometry Micro-CT |
| Fitter et al, 2008118 | Examine the effect of long-term imatinib or α-interferon therapy on bone of patients with CML. | CML | 29 (20M; 9F) | No differences between M and F. Before treatment: Trabecular bone volume was within the normal range in 15 patients, below normal in 10 patients, and exceeded the normal range in 4 patients (based on control values from a previous study122). | Posterior superior iliac spine trephine biopsies Histomorphometry |
| Teman et al, 201045 | Test the utility of digital imaging as an objective quantification method for both BM fibrosis and osteosclerosis. | PMF | 34 (19M; 15F) | Cohorts were pooled for analyses. All categories of MPN, except newly diagnosed CML, had significantly higher trabecular volume compared with controls. Trabecular volume was strikingly higher in PMF than in ET and PV. PMF had higher trabecular volume than MF that was secondary to other MPNs. There was no statistically significant relationship between JAK2 status and trabecular volume. | Posterior superior iliac spine trephine biopsies. Histomorphologic assessments of slides stained with hematoxylin and eosin and digitally scanned with a ScanScope XT system. |
| ET | 20 (9M; 11F) | ||||
| Post-ET MF | 14 (6M; 8F) | ||||
| PV | 14 (6M; 8F) | ||||
| Post-PV MF | 7 (3M; 4F) | ||||
| CML | 10 (6M; 4F) | ||||
| MPN-U (unclassifiable) | 22 (12M; 10F) | ||||
| Controls | 69 (41M; 28F) | ||||
| Farmer et al, 201546 | Assess bone geometry, bone mineral density, and microarchitecture in patients with MF. | MF (either primary MF or secondary to other MPN) | 18 (9M; 9F) | Cohorts were pooled for analyses. No significant differences between MF patients and controls regarding bone mineral density, geometry, and microarchitecture, despite manifestations of osteosclerosis observed in bone marrow biopsies of the patients. Bone stiffness and bone strength were similar between patients with MF and controls. | Lumbar spine and nondominant total hip region DXA. Nondominant distal radius and distal tibia HR-QCT. Measurements of biochemical markers for assessment of bone turnover. |
| Controls | 18 (9M; 9F) |
Studies without M/F indication did not report according to sex.
AMM, agnogenic myeloid metaplasia; CMPD, chronic myeloproliferative disease; F, female; HR-pQCT, high-resolution-peripheral quantitative computed tomography; IMF, idiopathic MF; M, male; micro-CT, micro-computed tomography; MM, megakaryocytic myelosis; ΜΜΜ, myelofibrosis with myeloid metaplasia.