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This paper reflects a summary of an article on the relationship between loss of bone mass and deficiency in vitamin D after hematopoietic stem cell transplantation (SCT). G. Massenkeil, C. Fiene, R. Michael, W. Reisinger and R. Arnold compiled the article in collaboration with Department of Internal Medicine, Division of Hematology and Oncology, Clinic for Nuclear Medicine and Institute of Radiology.
The major sub-topics to be summarized are fundamentals of Leukemia, Preparation for the study, Bone mineral density, and Vitamin D homeostasis.
Fundamentals of leukemia
According to the article, allogeneic stem cell transplantation (SCT) is capable of curing hematologic diseases like acute lymphoblastic leukemia (ALL), myelodysplastic syndrome (MDS), chronic myeloid leukemia (CML) and acute myelogenous leukemia (AML).
Observations of a study conducted on patients show a close relationship between osteoblasts, osteoclasts and hematopoietic stem cells. After the stem cell transplantation, the outcome is a reduction in the number of hematopoietic generating cells in a patient’s bone marrow for a stretched period.
Preparation for the study
The article shows that sixty-seven patients with ALL, AML, MDS and CML were prospectively studied after allogeneic SCT. Cyclosporine A (CsA) and methotrexate (MTX) were given to the patients as prophylaxis. Patients with donors who are not linked were injected with prednisone 0.5 mg/kg from day seven and 1.0 mg/kg from day 14 after allogeneic SCT.
First-line therapy of acute Graft-Versus-Host Disease (GVHD) was performed with a high-dose methylpredonisolone. It was prescribed that Persistent GVHD be suppressed with CsA, prednisone, azathioprine, cyclophosphamide and mycophenolate mofetil. In order to prevent hyper-catabolism, all patients received total parenteral nutrition starting on the day of SCT (energy 30-32 kcal/kg, fluid 2.5-3.0 I, carbohydrates 4-5 g/kg, amino acids 1-1.5g/kg, lipids 0.5 g/kg). This included 220 IU vitamin D and 660 mg calcium per day.
Bone mineral density
The article shows that lumber bone mineral density was measured by quantitative computed tomography scan. Bone mineral density was reduced before SCT in 49% of the patients. Pathologic bone mineral density values before SCT were mainly seen in patients with acute leukemia (ALL, AML and MDS), 55% of the patients with acute leukemia had osteopenia or osteoporosis before SCT. There was a significant loss of bone mass after SCT. Thirteen percent trabecular bone was lost after 6 months and 16.9% after 12 months.
Twenty-five patients underwent further bone mass density analysis after SCT, and only two patients had a further decrease in bone mass density. The two developed osteoporosis but only one presented chronic GVHD. Sixteen of 25 patients showed no variation in the values. Seven patients out of the 25 presented with increased bone mass density because after SCT, they were constantly supplied with alternatives options for oral calcium and vitamin D.
The article indicates that donor status, age, sex and amenorrhea had no significant impact on bone mineral density. Acute graft-versus-host-disease (GVHD) increases the chances of patients developing osteoporosis in short-term. In a short period like 6 months, bone mineral density in patients with acute GVHD decreased. However, after a long period, the situation came back to normalcy.
Vitamin D homeostasis
The article shows that before SCT, 39% of the patients had pathologic vitamin D plasma concentrations. It was noticed that all patients presented with hypovitaminosis immediately after SCT. Constantly reducing vitamin D concentrations were observed after the SCT. Disease, sex and donor status had no significant impact on vitamin D concentration.
According to the article, the study shows that after SCT, bone metabolism changes. It is also indicated that there is an increase in osteopenia after SCT. The study in the article shows that children with hematologic and oncologic malignancies have reduced bone mineral density after conventional chemotherapy.
Before SCT, bone mineral density and urinary excretion showed a great dependence in their causative diseases in with acute leukemia. The article indicates that rigorous chemotherapy seemingly, causes a major dangerous effect on bone metabolism.
Therapy that involves steroids also has a potential influence on bone mass. After allogeneic SCT, the loss of bone mass affected all patients except those who continually received treatment like supplement of vitamin D. It can only be speculated that the older age of patients with CML compared to those with acute leukemia made them more susceptible to change in bone mineral density due to the harmful effect of condition therapy.
Bone mineral density was lost early after allogeneic SCT. Loss of bone mineral density immediately after SCT is because of conditioning therapy characterized with high quantities of dosage. Lack of movement of hospitalized patients is notorious for causing rapid changes in calcium metabolism and decreased levels of vitamin D. Due to isolation, multiple infusion, general weakness and infections, physical activity is reduced during high-dose chemotherapy and bone marrow asplasia in patients.
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Osteopenia and osteoporosis are prevalent in adults who have experienced hematologic diseases caused by conventional therapy. Those who are mainly affected are Patients with rigorous pre-treatment exercise. A rapid bone loss is observed early after allogeneic SCT. Patients with higher bone mineral density before SCT comparatively lose more bone mineral density after SCT.