Bone mineral density in adult thalassaemias: a retrospective longitudinal study.

OBJECTIVES: In this study, we aim to evaluate the long-term impact of thalassaemia on bone mineral density (BMD) through sequential analysis, compare changes in BMD values between male and female patients and find any correlation between BMD and biochemical markers in the adult thalassaemia group. BMD is a bone mineral density test using dual-energy X-ray to measure calcium hydroxyapatite per unit of bone, reflecting bone strength. METHODS: We conducted a longitudinal retrospective observational cohort study to determine the changes in BMD values and biochemical parameters in adult thalassaemia patients. BMD was assessed at the lumbar spine (L1-L4) and proximal femora using Hologic's bone dual-energy X-ray absorptiometry. Five serial BMD values were retrieved from electronic records. Biochemical parameters, including serum calcium, phosphorus and 25-hydroxyvitamin D levels, were also assessed. RESULTS: A total of 108 patients (47 males and 61 females; median age: 44 years) with thalassaemia major 71 patients, intermedia 20 patients, haemoglobin E disease 14 patients and thalassaemia-alpha three patients were included. The incidence of low BMD in patients with thalassaemia increased from 64 to 74% over three decades of analysis. Females and thalassaemia major patients had lower hip BMD values and corresponding Z -scores. CONCLUSION: There is a progressive decline in BMD values in adult thalassaemia, which was apparent in female thalassaemia major patients. No changes in biochemical parameters, however, were observed over long-term assessments.

Mitapivat improves ineffective erythropoiesis and iron overload in adult patients with pyruvate kinase deficiency.

ABSTRACT: Pyruvate kinase (PK) deficiency is a rare, hereditary disease characterized by chronic hemolytic anemia. Iron overload is a common complication regardless of age, genotype, or transfusion history. Mitapivat, an oral, allosteric PK activator, improves anemia and hemolysis in adult patients with PK deficiency. Mitapivat's impact on iron overload and ineffective erythropoiesis was evaluated in adults with PK deficiency who were not regularly transfused in the phase 3 ACTIVATE trial and long-term extension (LTE) (#NCT03548220/#NCT03853798). Patients in the LTE received mitapivat throughout ACTIVATE/LTE (baseline to week 96; mitapivat-to-mitapivat [M/M] arm) or switched from placebo (baseline to week 24) to mitapivat (week 24 to week 96; placebo-to-mitapivat [P/M] arm). Changes from baseline in markers of iron overload and erythropoiesis were assessed to week 96. Improvements in hepcidin (mean, 4770.0 ng/L; 95% confidence interval [CI], -1532.3 to 11 072.3), erythroferrone (mean, -9834.9 ng/L; 95% CI, -14 328.4 to -5341.3), soluble transferrin receptor (mean, -56.0 nmol/L; 95% CI, -84.8 to -27.2), and erythropoietin (mean, -32.85 IU/L; 95% CI, -54.65 to -11.06) were observed in the M/M arm (n = 40) from baseline to week 24, sustained to week 96. No improvements were observed in the P/M arm (n = 40) to week 24; however, upon transitioning to mitapivat, improvements similar to those observed in the M/M arm were seen. Mean changes from baseline in liver iron concentration by magnetic resonance imaging at week 96 in the M/M arm and the P/M arm were -2.0 mg Fe/g dry weight (dw; 95% CI, -4.8 to -0.8) and -1.8 mg Fe/g dw (95% CI, -4.4 to 0.80), respectively. Mitapivat is the first disease-modifying pharmacotherapy shown to have beneficial effects on iron overload and ineffective erythropoiesis in patients with PK deficiency. This trial was registered at www.ClinicalTrials.gov as #NCT03548220 (ACTIVATE) and #NCT03853798 (LTE).