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Bone density loss during treatment of chronic GVHD
J M Stern1, C H Chesnut, B Bruemmer
1Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA.
Insights
Patients treated for chronic graft-versus-host disease (GVHD) show increased bone turnover and a significant risk of osteoporosis. Early preventive measures are recommended to mitigate bone loss and potential fractures.
Area of Science:
- Bone Metabolism and Endocrinology
- Hematology and Oncology
- Immunology
Background:
- Chronic graft-versus-host disease (GVHD) is a significant complication following allogeneic stem cell transplantation.
- Immunosuppressive therapy, including prednisone and cyclosporin A (CsA), is standard for managing chronic GVHD.
- The impact of chronic GVHD and its treatment on skeletal health remains an area of concern.
Purpose of the Study:
- To evaluate biochemical markers of skeletal turnover in patients with chronic GVHD.
- To assess changes in bone mineral density (BMD) over time in these patients.
- To identify risk factors for bone loss and osteoporosis in chronic GVHD patients undergoing immunosuppressive therapy.
Main Methods:
- Biochemical assessment of serum and urine markers related to bone metabolism (e.g., 1,25(OH)2D, calcium, hydroxyproline, magnesium).
- Bone mineral density measurement using single and dual photon absorptiometry and dual energy X-ray absorptiometry.
- Longitudinal evaluation of nine adult patients at immunosuppressive therapy initiation and nine months later.
Main Results:
- Decreased serum 1,25-dihydroxycholecalciferol (1,25(OH)2D) levels were observed at baseline and follow-up.
- Elevated urine hydroxyproline and calcium levels at baseline indicated increased bone resorption, decreasing to high normal by follow-up.
- Significant bone mineral density loss was detected in males and females over the nine-month study period.
Conclusions:
- Patients with chronic GVHD treated with prednisone and CsA exhibit increased bone turnover and a high risk of osteoporosis.
- Biochemical abnormalities and bone loss suggest a need for early intervention.
- Preventive strategies, such as hormone replacement therapy in females, should be considered early post-transplant to preserve bone health.
Abstract:
Nine adult patients 31-47 (median 39) years of age treated with prednisone and cyclosporin A (CsA) for chronic graft-versus-host disease (GVHD) were evaluated for biochemical factors associated with skeletal turnover at initiation of immunosuppressive therapy (3 months after marrow transplant) and 9 months later (follow-up). Absorptiometry studies of the wrist and lumbar spine were also performed. Serum levels of 1,25-dihydroxycholecalciferol (1,25(OH)2D) were decreased at enrollment, particularly in the six males. Values for all nine patients remained low at follow-up. Levels of serum 25-hydroxycholecalciferol (25(OH)D), parathyroid hormone, and ionized calcium were normal at enrollment and follow-up. Mean urine hydroxyproline and calcium levels were elevated at enrollment, suggesting increased bone resorption; the mean values decreased to the high normal range at follow-up. Urine magnesium excretion was elevated in eight of nine patients at baseline and remained elevated at follow-up in three of eight evaluable patients. Single and dual photon absorptiometry of the wrist and spine, respectively, and dual energy X-ray absorptiometry of the spine, were utilized to evaluate bone mineral density over time. The precision of these tests was, respectively, +/- 3.5%, +/- 3.1% and +/- 1.0%. Results showed a significant ( > 2.5 times the precision) decrease over 9 months in bone mineral density in three of five evaluable males and all three females. The findings indicate increased collagen and bone turnover, increased urinary magnesium and calcium excretion and a significant risk of osteoporosis in patients receiving treatment for chronic GVHD. Preventive measures, including gonadal hormone replacement in females, should be initiated early after transplantation. Further studies are needed to identify patients at highest risk of bone loss and to monitor the effects of preventive therapy.