Prevalence of Osteoporosis in Myelodysplastic Syndrome Patients and Association with Cytopenias

Background :Perturbations of the osteo-hematopoietic niche architecture disrupt tissue homeostasis and can promote malignant diseases such as myelodysplastic syndromes (MDS).

Recently an increased risk of osteoporosis in patients with CHIP has been observed after adjusting on usual risk factors for osteoporosis and in mouse models DnmT3a mutation cause a reduction in bone mass.

However, little is known on the clinical presentation of osteoporosis in MDS patients. Here we report the results of a prospective cohort study of bone mass evaluation in newly diagnosed MDS patients.

Methods : All patients with newly-diagnosed MDS or CMML (proved by bone marrow aspirate) were prospectively enrolled since January 2020 after informed consent. Bone mass evaluation was performed by conventional radiography of dorsal and lumbar rachis and bone mineral density was measured by a HOLOGIC® device at the upper extremity of the femur and the rachis. Osteoporosis risk factor were collected by a rheumatologist. After analysis of osteoporosis biomarker and biological MDS evaluation, if the diagnosis of osteoporosis was established, specific treatment were proposed. Avaible bone marrow biopsies were analysed by RAMAN microspectrosopy and compared to healthy bone marrow analysis specimens.

Results : At data cut off (06/06/2022)108 pts were enrolled and evaluable for bone mineral density. Median age was 77 years [55-99] and 45.4% were female. WHO classification included MDS-MLD, MDS-MLD, MDS-RS-SLD, MDS-RS-MLD, 5Q-, MDS-EB1, MDS-EB2, CMML and AML (with 20-30% blast) in 10.2%,16.7%, 10.7%, 5.6%, 10.2%, 14.8%, 5.6%, 23.2% and 2.6% respectively. IPSS-R was very low, low, intermediate, high and very high in 20.4%, 51%, 19.4%, 8.3%, 1% respectively.

Prior to the bone assessment, 15 pts had already a diagnosis of osteoporosis and among them 10 had previously received bisphosphonates. At the time of the bone assessment, 57 additional pts (52.8%) were diagnosed with osteoporosis including 22 males et 35 females and 30 pts (27.8%) had a prevalent osteoporotic vertebral fracture. In our cohort, prevalence of osteoporosis seem to increase with R-IPSS score with 49.4 %, 57.1% and 70% in low, intermediate, and high-risk, pts respectively, near significativity (p=0.052).

After univariate analysis neither age (p=0.46) , 25 OH –vitamine D (p=0.07), ferritine (p=0.53), EPO (p=0.45), nor R-IPSS score (p=0.2) were associated with osteoporosis. However osteoporotic pts had significantly lower hemoglobin levels (9.7 vs 10.3 g/dL, p=0.04) and platelet counts (215 vs 170 G/L, p=0.05). After multivariate analysis, only female gender remained statistically associated with osteoporosis (p=0.01).

After initial evaluation among the 57 pts with ostoporosis, 53 pts (49% of the cohort) were treated with intravenous bisphosphonates (2 pts refused and 2 had a contraindication).

Analysis of avaible bone marrow biopsies (n=8) by Raman microspectoscopy at the center of trabecula showed defects in the bone marrow matrix in MDS pts in comparison to healthy specimens (n=18) with an increase in the hydoxylation of proline suggesting degradation of collagen type I in MDS bone. (figure 1)

Conclusion : We found a high prevalence of osteoporosis in 52.3% of prospective, newly diagnosed MDS pts with 27.8% of pts with osteoporotic vertebral fracture. More profound cytopenias seem to be associated with an increased risk of osteoporosis prevalence underlying the impact of the osteo-hematopoietic niche in the physiopathology of MDS. An update of this study will be presented