Characterization and Risk Factor Analysis of Osteoporosis in a Large Cohort of Patients with Chronic Graft-versus-Host Disease

Abstract

The NIH Chronic Graft-versus-Host Disease (cGVHD) Consensus Project Ancillary and Supportive Care Guidelines recommend annual assessment of bone mineral density (BMD) to monitor bone health. The study of osteoporosis in patients with cGVHD has been limited to small numbers of patients and the guidelines are based on experiences in other chronic diseases and expert opinion. We hypothesized that the prevalence of osteoporosis is high in a cohort of 258 patients with moderate to severe cGVHD due to prolonged exposure to risk factors for osteoporosis after allogeneic hematopoietic stem cell transplantation. We defined osteoporosis using BMD criteria (T-score ≤ -2.5) at three anatomical sites (femoral neck – FN, lumbar spine – LS, total hip – TH) and characterized risk factors through univariate and multivariate analyses. We found that low body weight (FN p<0.0001, LS p=0.0002, TH p<0.0001), malnutrition (FN p=0.0002, LS p=0.03, TH p=0.0076), higher platelet count (FN p=0.0065, TH p=0.0025), higher average NIH organ score (FN p=0.038), higher prednisone dose (LS p=0.032), lower complement component 3 (LS p=0.0073), and physical inactivity (FN p=0.01) were associated with osteoporosis in one or more site. T-scores were significantly lower in the FN than in the other two sites (p<0.0001 for both). The prevalence of osteoporosis and osteopenia was high (17% and 60%, respectively), supporting current recommendations for frequent monitoring of BMD. The association of higher platelet count in cGVHD patients with osteoporosis has not been previously reported and presents a new area of interest in the study of osteoporosis after allogeneic hematopoietic stem cell transplantation.

Impaired Bone Mineral Density in Pediatric Patients with Chronic Graft-versus-Host Disease

“…Perhaps, this provides an explanation for our finding that “older age” (pubertal) at the time of cGVHD diagnosis was correlated with presence of VCF. Not surprisingly, in our patient cohort, the femoral neck, a site rich in trabecular bone, was the most frequently affected location, consistent with what has been reported in adult patients with cGVHD 4, 12, 33, 36 . Also, corticosteroids have been shown to exert greater effects on trabecular than cortical bone, which could provide another reason for the observed BMD impairment pattern observed in AHSCT recipients on our study and others 13, 37 .…”

“…Similarly, the use of systemic corticosteroids has been strongly linked to BMD impairment in pediatric AHSCT recipients 4, 10, 15 . When comparing our pediatric versus adult cGVHD cohort (concurrently enrolled on the same study) we observed a higher rate of significant BMD impairment, with DEXA z-score ≤-2 at three sites in 39% of pediatric versus17% of adult patients, despite both groups having a similarly high prevalence of severe cGVHD 33 . Pediatric AHSCT recipients are particularly vulnerable to bone health impairments.…”

Blood factors as biomarkers in osteoporosis: points from the COVID-19 era

“…Thus, it is straightforward to understand the presence of a close relationship between hematopoiesis and bone remodeling, considering that several studies found that PLTs, the cytoplasmic fragments derived from megakaryocytes, have a critical role in skeletal homeostasis, modulating bone formation and resorption [ 19 , 20 ]. An increasing number of clinical studies evaluated the relationship between PLTs and OP status based on BMD, considering and comparing healthy, osteopenic, and OP subjects [ 21. , 22.…”

Late Effects Screening Guidelines after Hematopoietic Cell Transplantation (HCT) for Hemoglobinopathy: Consensus Statement from the Second Pediatric Blood and Marrow Transplant Consortium International Conference on Late Effects after Pediatric HCT

“…GVHD manifestations are similar to those in patients with malignant disorders, and incidence and severity vary according to the graft source, HLA compatibility, and patient age [43]. Depending on its severity, chronic GVHD can negatively affect long-term quality of life and requires monitoring and intervention for control [44,45]. The incidence of malignant disorders after HCT for thalassemia is <10 per 100,000 per year and does not appear to be higher than in patients with β-thalassemia major that are not transplanted [46,47].…”