Zoledronic Acid Increases Bone Mineral Density in Patients with Thalassemia Intermedia-Induced Osteoporosis Regardless of the Incessant Bone Marrow Expansion.
Bibliographic record
Abstract
Abstract Osteoporosis represents an important cause of morbidity in adult patients with thalassemia. Its pathogenesis is multifactorial, and includes mainly bone marrow expansion, endocrine dysfunction and iron overload. Patients with thalassaemia intermedia (TI) seem to have a more expanded bone marrow with pressure on cortical bone, which causes pain and bone loss in several cases. The measurement of soluble transferrin receptor (sTfR) and erythropoietin (Epo) in the serum is considered as accurate marker of erythropoietic activity in thalassemia. Bisphosphonates are potent inhibitors of osteoclast activity and have been used for the management of thalassemia-induced osteoporosis. The aim of this study was to evaluate the effect of zoledronic acid, the most potent aminobisphosphonate, on bone mineral density (BMD) of patients with TI and explore possible correlations with bone marrow expansion and erythropoietic activity. Thirty-five patients with TI and osteopenia or osteoporosis (13M/22F, median age 45 years) were evaluated. Twenty-three were randomized to receive zoledronic acid, 4 mg, IV, every 3 months (n=12) or every 6 months (n=11) for one year, while 12 patients received placebo every 3 months. There was no difference in terms of the presence of gonadal dysfunction between the three studied groups. BMD of the lumbar spine (L), femoral neck and forearm was determined in all patients, using DEXA, before and 12 months after treatment. Bone marrow expansion was assessed by the measurement of sTfR and Epo serum levels, using an ELISA methodology (R&D Systems, Minneapolis, MN, USA), before and 12 months post zoledronic acid or placebo administration. In all patients markers of bone remodelling, such as C-telopeptide of collagen type-I (CTX) and bone specific alkaline phosphatase (bALP) were also measured by ELISA (Nordic Bioscience Diagnostics, Herlev, Denmark, and Quidel, San Diego, CA, USA, respectively). Patients were asked to quantify their degree of bone pain on Huskisson’s visual analogue scale and the McGill-Melzack scoring system before and 12 months post-therapy. All patients had increased values of sTfR, Epo, CTX, and bALP compared with 40 controls of similar age and gender (p<0.001). Patients who received zoledronic acid showed a significant increase in their L-BMD (p=0.01), which was accompanied by a dramatic reduction in CTX and bALP values ((p<0.001). There was no difference in terms of L-BMD changes between zoledronic acid groups. Placebo group showed an aggravation of L-BMD (p=0.041) and markers of bone remodelling at 12 months. No other changes were observed in the BMD of other sites. Zoledronic acid reduced bone pain, which remained stable in placebo group during the study period. There was only weak correlation between baseline sTfR levels and L-BMD, while there was no correlation between Epo or hemolytic parameters (indirect bilirubin, reticulocytes counts, and LDH) with BMD of all studied sites. Serum sTfR and Epo values showed a significant elevation after 12 months of therapy in all studied groups (p<0.01, p<0.02, and p<0.01, respectively); this elevation was irrespective of the L-BMD changes. This study suggests that the increase of BMD produced by zoledronic acid in TI is irrespective of the continuous increase of bone marrow expansion, which is considered a major cause of bone loss in this hemoglobinopathy.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".