-
Hemolytic disease of the fetus and newborn: systematic literature review of the antenatal landscape.BMC Pregnancy and Childbirth Jan 2023Prevention of pregnancy-related alloimmunization and the management of hemolytic disease of the fetus and newborn (HDFN) has significantly improved over the past...
BACKGROUND
Prevention of pregnancy-related alloimmunization and the management of hemolytic disease of the fetus and newborn (HDFN) has significantly improved over the past decades. Considering improvements in HDFN care, the objectives of this systematic literature review were to assess the prenatal treatment landscape and outcomes of Rh(D)- and K-mediated HDFN in mothers and fetuses, to identify the burden of disease, to identify evidence gaps in the literature, and to provide recommendations for future research.
METHODS
We performed a systematic search on MEDLINE, EMBASE and clinicaltrials.gov. Observational studies, trials, modelling studies, systematic reviews of cohort studies, and case reports and series of women and/or their fetus with HDFN caused by Rhesus (Rh)D or Kell alloimmunization. Extracted data included prevalence; treatment patterns; clinical outcomes; treatment efficacy; and mortality.
RESULTS
We identified 2,541 articles. After excluding 2,482 articles and adding 1 article from screening systematic reviews, 60 articles were selected. Most abstracted data were from case reports and case series. Prevalence was 0.047% and 0.006% for Rh(D)- and K-mediated HDFN, respectively. Most commonly reported antenatal treatment was intrauterine transfusion (IUT; median frequency [interquartile range]: 13.0% [7.2-66.0]). Average gestational age at first IUT ranged between 25 and 27 weeks. weeks. This timing is early and carries risks, which were observed in outcomes associated with IUTs. The rate of hydrops fetalis among pregnancies with Rh(D)-mediated HDFN treated with IUT was 14.8% (range, 0-50%) and 39.2% in K-mediated HDFN. Overall mean ± SD fetal mortality rate that was found to be 19.8%±29.4% across 19 studies. Mean gestational age at birth ranged between 34 and 36 weeks.
CONCLUSION
These findings corroborate the rareness of HDFN and frequently needed intrauterine transfusion with inherent risks, and most births occur at a late preterm gestational age. We identified several evidence gaps providing opportunities for future studies.
Topics: Female; Humans; Pregnancy; Erythroblastosis, Fetal; Hydrops Fetalis; Hemolysis; Blood Transfusion, Intrauterine; Fetus
PubMed: 36611144
DOI: 10.1186/s12884-022-05329-z -
JAMA Network Open Oct 2023Sickle cell disease (SCD) is a monogenic disorder, yet clinical outcomes are influenced by additional genetic factors. Despite decades of research, the genetics of SCD... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Sickle cell disease (SCD) is a monogenic disorder, yet clinical outcomes are influenced by additional genetic factors. Despite decades of research, the genetics of SCD remain poorly understood.
OBJECTIVE
To assess all reported genetic modifiers of SCD, evaluate the design of associated studies, and provide guidelines for future analyses according to modern genetic study recommendations.
DATA SOURCES
PubMed, Web of Science, and Scopus were searched through May 16, 2023, identifying 5290 publications.
STUDY SELECTION
At least 2 reviewers identified 571 original, peer-reviewed English-language publications reporting genetic modifiers of human SCD phenotypes, wherein the outcome was not treatment response, and the comparison was not between SCD subtypes or including healthy controls.
DATA EXTRACTION AND SYNTHESIS
Data relevant to all genetic modifiers of SCD were extracted, evaluated, and presented following STREGA and PRISMA guidelines. Weighted z score meta-analyses and pathway analyses were conducted.
MAIN OUTCOMES AND MEASURES
Outcomes were aggregated into 25 categories, grouped as acute complications, chronic conditions, hematologic parameters or biomarkers, and general or mixed measures of SCD severity.
RESULTS
The 571 included studies reported on 29 670 unique individuals (50% ≤ 18 years of age) from 43 countries. Of the 17 757 extracted results (4890 significant) in 1552 genes, 3675 results met the study criteria for meta-analysis: reported phenotype and genotype, association size and direction, variability measure, sample size, and statistical test. Only 173 results for 62 associations could be cross-study combined. The remaining associations could not be aggregated because they were only reported once or methods (eg, study design, reporting practice) and genotype or phenotype definitions were insufficiently harmonized. Gene variants regulating fetal hemoglobin and α-thalassemia (important markers for SCD severity) were frequently identified: 19 single-nucleotide variants in BCL11A, HBS1L-MYB, and HBG2 were significantly associated with fetal hemoglobin (absolute value of Z = 4.00 to 20.66; P = 8.63 × 10-95 to 6.19 × 10-5), and α-thalassemia deletions were significantly associated with increased hemoglobin level and reduced risk of albuminuria, abnormal transcranial Doppler velocity, and stroke (absolute value of Z = 3.43 to 5.16; P = 2.42 × 10-7 to 6.00 × 10-4). However, other associations remain unconfirmed. Pathway analyses of significant genes highlighted the importance of cellular adhesion, inflammation, oxidative and toxic stress, and blood vessel regulation in SCD (23 of the top 25 Gene Ontology pathways involve these processes) and suggested future research areas.
CONCLUSIONS AND RELEVANCE
The findings of this comprehensive systematic review and meta-analysis of all published genetic modifiers of SCD indicated that implementation of standardized phenotypes, statistical methods, and reporting practices should accelerate discovery and validation of genetic modifiers and development of clinically actionable genetic profiles.
Topics: Humans; Fetal Hemoglobin; alpha-Thalassemia; Anemia, Sickle Cell; Genotype; Genetic Variation
PubMed: 37851445
DOI: 10.1001/jamanetworkopen.2023.37484 -
The Cochrane Database of Systematic... Sep 2022Sickle cell disease (SCD) is one of the most common inherited diseases worldwide. It is associated with lifelong morbidity and a reduced life expectancy. Hydroxyurea... (Review)
Review
BACKGROUND
Sickle cell disease (SCD) is one of the most common inherited diseases worldwide. It is associated with lifelong morbidity and a reduced life expectancy. Hydroxyurea (hydroxycarbamide), an oral chemotherapeutic drug, ameliorates some of the clinical problems of SCD, in particular that of pain, by raising foetal haemoglobin (HbF). This is an update of a previously published Cochrane Review.
OBJECTIVES
The aims of this review are to determine through a review of randomised or quasi-randomised studies whether the use of hydroxyurea in people with SCD alters the pattern of acute events, including pain; prevents, delays or reverses organ dysfunction; alters mortality and quality of life; or is associated with adverse effects. In addition, we hoped to assess whether the response to hydroxyurea in SCD varies with the type of SCD, age of the individual, duration and dose of treatment, and healthcare setting.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Haemoglobinopathies Register, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched online trial registries. The date of the most recent search was 17 February 2022.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials (RCTs and quasi-RCTs), of one month or longer, comparing hydroxyurea with placebo or standard therapy in people with SCD.
DATA COLLECTION AND ANALYSIS
Authors independently assessed studies for inclusion, carried out data extraction, assessed the risk of bias and assessed the quality of the evidence using GRADE.
MAIN RESULTS
We included nine RCTs recruiting 1104 adults and children with SCD (haemoglobin SS (HbSS), haemoglobin SC (HbSC) or haemoglobin Sβºthalassaemia (HbSβºthal) genotypes). Studies lasted from six to 30 months. We judged the quality of the evidence for the first two comparisons below as moderate to low as the studies contributing to these comparisons were mostly large and well-designed (and at low risk of bias); however, the evidence was limited and imprecise for some outcomes such as quality of life, deaths during the studies and adverse events, and the results are applicable only to individuals with HbSS and HbSβºthal genotypes. We judged the quality of the evidence for the third and fourth comparisons to be very low due to the limited number of participants, the lack of statistical power (both studies were terminated early with approximately only 20% of their target sample size recruited) and the lack of applicability to all age groups and genotypes. Hydroxyurea versus placebo Five studies (784 adults and children with HbSS or HbSβºthal) compared hydroxyurea to placebo; four recruited individuals with only severe disease and one recruited individuals with all disease severities. Hydroxyurea probably improves pain alteration (using measures such as pain crisis frequency, duration, intensity, hospital admissions and opoid use) and life-threatening illness, but we found no difference in death rates (10 deaths occurred during the studies, but the rates did not differ by treatment group) (all moderate-quality evidence). Hydroxyurea may improve measures of HbF (low-quality evidence) and probably decreases neutrophil counts (moderate-quality evidence). There were no consistent differences in terms of quality of life and adverse events (including serious or life-threatening events) (low-quality evidence). There were fewer occurrences of acute chest syndrome and blood transfusions in the hydroxyurea groups. Hydroxyurea and phlebotomy versus transfusion and chelation Two studies (254 children with HbSS or HbSβºthal also with risk of primary or secondary stroke) contributed to this comparison. There were no consistent differences in terms of pain alteration, death or adverse events (low-quality evidence) or life-threatening illness (moderate-quality evidence). Hydroxyurea with phlebotomy probably increased HbF and decreased neutrophil counts (moderate-quality evidence), but there were more occurrences of acute chest syndrome and infections. Quality of life was not reported. In the primary prevention study, no strokes occurred in either treatment group but in the secondary prevention study, seven strokes occurred in the hydroxyurea and phlebotomy group (none in the transfusion and chelation group) and the study was terminated early. Hydroxyurea versus observation One study (22 children with HbSS or HbSβºthal also at risk of stoke) compared hydroxyurea to observation. Pain alteration and quality of life were not reported. There were no differences in life-threatening illness, death (no deaths reported in either group) or adverse events (very low-quality evidence). We are uncertain if hydroxyurea improves HbF or decreases neutrophil counts (very low-quality evidence). Treatment regimens with and without hydroxyurea One study (44 adults and children with HbSC) compared treatment regimens with and without hydroxyurea. Pain alteration, life-threatening illness and quality of life were not reported. There were no differences in death rates (no deaths reported in either group), adverse events or neutrophil levels (very low-quality evidence). We are uncertain if hydroxyurea improves HbF (very low-quality evidence).
AUTHORS' CONCLUSIONS
There is evidence to suggest that hydroxyurea may be effective in decreasing the frequency of pain episodes and other acute complications in adults and children with sickle cell anaemia of HbSS or HbSβºthal genotypes and in preventing life-threatening neurological events in those with sickle cell anaemia at risk of primary stroke by maintaining transcranial Doppler velocities. However, there is still insufficient evidence on the long-term benefits of hydroxyurea, particularly with regard to preventing chronic complications of SCD, or recommending a standard dose or dose escalation to maximum tolerated dose. There is also insufficient evidence about the long-term risks of hydroxyurea, including its effects on fertility and reproduction. Evidence is also limited on the effects of hydroxyurea on individuals with the HbSC genotype. Future studies should be designed to address such uncertainties.
Topics: Acute Chest Syndrome; Adult; Anemia, Sickle Cell; Antisickling Agents; Child; Hemoglobin, Sickle; Humans; Hydroxyurea; Pain; Stroke
PubMed: 36047926
DOI: 10.1002/14651858.CD002202.pub3 -
Heliyon Nov 2021Treatment for polycystic ovary syndrome (PCOS) usually initiates with a series of lifestyle modifications such as diet, weight loss, and exercise.
BACKGROUND
Treatment for polycystic ovary syndrome (PCOS) usually initiates with a series of lifestyle modifications such as diet, weight loss, and exercise.
AIMS
We, therefore, conducted this meta-analysis to systematically review and evaluate the possible benefits of LGD on a range of anthropometric, clinical, and biochemical parameters in women with PCOS.
METHODS
We performed a systematic search through major indexing databases, including Scopus, Pubmed/Medline, ISI web of science, Embase, Cochrane central, and CINAHL (1966-April 30, 2021) using key concepts of PCOS.
RESULTS
Of 935 initial publications, 542 remain after duplicates removal. Then, 141 records were removed at the title and abstract screening level. After excluding 392 literatures, we finally included 8 articles. The final selected studies included 412 overweight and obese individuals with PCOS (207 cases in LGID group and 205 patients in comparators) with a mean age of 21-32 years. Measured emotional health (3 studies, 132 participants, SMD: -1.97; 95%CI:-3.54, -0.40, = 0.01, = 89%) and body hair (3 studies, 132 participants, SMD: -0.40; 95%CI:-0.46, -0.35, < 0.0001, = 0%), were found to be significantly lower in women in LGD vs control diet groups. Moreover, infertility (3 studies, 132 participants, SMD: 1.45; 95%CI: 0.30, 2.61, = 0.01, = 79%) was significantly higher in women in LGD vs control diet groups.
CONCLUSION
The present meta-analysis has shown that LGD may play a significant role in reducing the risk and improving the clinical and biochemical features of PCOS. So far the evidences for choosing the best dietary modalities for PCOS are not strong to make a definite recommendation.
PubMed: 34820542
DOI: 10.1016/j.heliyon.2021.e08338 -
Journal of Reproduction & Infertility 2023Cell-free fetal DNA (cffDNA) is a novel screening method for fetal aneuploidy that facilitated non-invasive prenatal testing (NIPT) through analysis of cffDNA in... (Review)
Review
BACKGROUND
Cell-free fetal DNA (cffDNA) is a novel screening method for fetal aneuploidy that facilitated non-invasive prenatal testing (NIPT) through analysis of cffDNA in maternal plasma. However, despite increased sensitivity, it has a number of limitations that may complicate of its results interpretation. Therefore, elucidating factors affecting fetal fraction, as a critical limitation, guides its clinical application.
METHODS
In this report, systematic search was carried out through PubMed, Web of Science, and Scopus databases until February 11, 2022 by using keywords consist of "noninvasive prenatal screening", "NIPT", "noninvasive prenatal", "cell free DNA" and "fetal fraction". The articles were screened for eligibility criteria before data extraction.
RESULTS
A total of 39 eligible studies, most published between 2010 and 2020, were included. Based on the results of studies, a negative correlation between maternal age and BMI/body weight with fetal fraction was found. Furthermore, LDL, cholesterol, triglyceride level, metformin, heparin and enoxaparin therapy, hemoglobin-related hemoglobinopathies, and physical activity showed to have negative associations. Interestingly, it seems the ethnicity of patients from South and East Asia has a correlation with fetal fraction compared to Caucasians. Positive correlation was observed between gestational age, free β-hCG, PAPP-A, living in high altitude, and twin pregnancy.
CONCLUSION
Considering each factor, there was significant inconsistency and controversy regarding their impact on outcomes. Indeed, multiple factors can influence the accuracy of NIPS results, and it is worth noting that the impact of these factors may vary depending on the individual's ethnic background. Therefore, it is important to recognize that NIPS remains a screening test, and comprehensive pre- and post-NIPS counseling should be conducted as part of standard clinical practice.
PubMed: 38164433
DOI: 10.18502/jri.v24i4.14149 -
Journal of Clinical Medicine Dec 2021In the last half century, the life expectancy of beta-thalassemia patients has strikingly increased mostly due to regular blood transfusions and chelation treatments.... (Review)
Review
In the last half century, the life expectancy of beta-thalassemia patients has strikingly increased mostly due to regular blood transfusions and chelation treatments. The improved survival, however, has allowed for the emergence of comorbidities, such as hearing loss, with a non-negligible impact on the patients' quality of life. This thorough review analyzes the acquired knowledge regarding hearing impairment in this hereditary hemoglobinopathy, aiming at defining its prevalence, features, course, and possible disease- or treatment-related pathogenic factors. Following PRISMA criteria, we retrieved 60 studies published between 1979 and 2021. Diagnostic tools and criteria, forms of hearing impairment, correlations with beta-thalassemia phenotypes, age and sex, chelation treatment and laboratory findings including iron overload, were carefully searched, analyzed and summarized. In spite of the relatively high number of studies in the last 40 years, our knowledge is rather limited, and large prospective studies with homogeneous diagnostic tools and criteria are required to define all the aforementioned issues. According to the literature, the overall prevalence rate of hearing impairment is 32.3%; age, sex, and laboratory findings do not seem to correlate with hearing deficits, while the weak relationship with clinical phenotype and chelation treatment seems to highlight the presence of further yet to be identified pathogenic factors.
PubMed: 35011846
DOI: 10.3390/jcm11010102 -
Frontiers in Medicine 2021This systematic review aimed to provide an overview of the clinical profile and outcome of COVID-19 infection in patients with hemoglobinopathy. The rate of COVID-19...
This systematic review aimed to provide an overview of the clinical profile and outcome of COVID-19 infection in patients with hemoglobinopathy. The rate of COVID-19 mortality and its predictors were also identified. A systematic search was conducted in accordance with PRISMA guidelines in five electronic databases (PubMed, Scopus, Web of Science, Embase, WHO COVID-19 database) for articles published between 1st December 2019 to 31st October 2020. All articles with laboratory-confirmed COVID-19 cases with underlying hemoglobinopathy were included. Methodological quality was assessed using the Joanna Briggs Institute (JBI) critical appraisal checklists. Thirty-one articles with data on 246 patients with hemoglobinopathy were included in this review. In general, clinical manifestations of COVID-19 infection among patients with hemoglobinopathy were similar to the general population. Vaso-occlusive crisis occurred in 55.6% of sickle cell disease patients with COVID-19 infection. Mortality from COVID-19 infection among patients with hemoglobinopathy was 6.9%. After adjusting for age, gender, types of hemoglobinopathy and oxygen supplementation, respiratory (adj OR = 89.63, 95% CI 2.514-3195.537, = 0.014) and cardiovascular (adj OR = 35.20, 95% CI 1.291-959.526, = 0.035) comorbidities were significant predictors of mortality. Patients with hemoglobinopathy had a higher mortality rate from COVID-19 infection compared to the general population. Those with coexisting cardiovascular or respiratory comorbidities require closer monitoring during the course of illness. More data are needed to allow a better understanding on the clinical impact of COVID-19 infections among patients with hemoglobinopathy. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020218200.
PubMed: 34722593
DOI: 10.3389/fmed.2021.757510 -
Archives of Physical Medicine and... Jun 2022To examine physical impairments and physical function in children and adolescents with sickle cell disease (SCD). (Review)
Review
OBJECTIVE
To examine physical impairments and physical function in children and adolescents with sickle cell disease (SCD).
DATA SOURCES
PubMed, Embase (embase.com), Cumulative Index to Nursing and Allied Health (EBSCO), Cochrane Central Register of Controlled Trials (Wiley), and Dissertations and Theses (ProQuest) were searched from January 1, 1990, to September 25, 2020. References retrieved were required to include a term for SCD and a term for physical impairments or physical function. Results were limited to articles with children and adolescents and in the English language.
STUDY SELECTION
A total of 3054 nonduplicate articles were independently screened by 2 reviewers, resulting in 240 articles for full-text review. The full-text review, performed by 2 independent reviewers, resulted in 67 articles.
DATA EXTRACTION
Data were extracted from each full text to a custom Excel document by a single reviewer and were verified by a secondary reviewer.
DATA SYNTHESIS
The studies identified in this systematic review offer evidence that children and adolescents with SCD demonstrate physical impairments and physical function limitations compared with control participants as noted by varying percentages in deficits up to 19%-58% in muscle and bone composition and/or symptoms, muscle strength, cardiopulmonary function, motor performance, physical activity, and physical function domains of quality of life questionnaires.
CONCLUSIONS
Children and adolescents with SCD present with physical impairments and physical function limitations. Scientists and clinicians should consider developing collaborative standards to define and objectively measure physical impairment and function in this population to comprehensively examine the underlying factors that contribute to physical impairments and function.
Topics: Adolescent; Anemia, Sickle Cell; Child; Exercise; Humans; Quality of Life
PubMed: 34592159
DOI: 10.1016/j.apmr.2021.08.022 -
Clinica Chimica Acta; International... Nov 2020Hemolysis is one of the main pathophysiological characteristics of sickle cell disease (SCD) and might cause or could be the result of oxidative stress. Antioxidants are... (Review)
Review
Hemolysis is one of the main pathophysiological characteristics of sickle cell disease (SCD) and might cause or could be the result of oxidative stress. Antioxidants are studied in SCD due to their potential to ensure redox balance and minimize deleterious effects on erythrocyte membranes. The objective of this systematic review was to evaluate the efficacy of antioxidant nutrient supplementation on reducing hemolysis in SCD patients through randomized clinical trials. We conducted our study according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses and the Cochrane Handbook for Systematic Reviews of Interventions investigating whether antioxidants could improve the hemolytic status of SCD patients. This study included 587 articles published until April 2020. We reduced this pool to 12 articles by excluding duplicates, reviews, comments, and studies with non-human subjects. Omega-3 fatty acids, vitamin A, and zinc were the antioxidants that reportedly improved the indirect hemolysis parameters such as hemoglobin, hematocrit, mean corpuscular volume, or red blood cells. High-dose vitamin C and E supplementation worsened hemolysis, causing increased reticulocytes, lactate dehydrogenase, indirect bilirubin, and haptoglobin. More intervention studies especially high-quality controlled randomized clinical trials are needed to investigate the effects of antioxidant nutrients in reducing hemolysis in SCD.
Topics: Anemia, Sickle Cell; Antioxidants; Erythrocytes; Hemolysis; Humans; Nutrients
PubMed: 32673671
DOI: 10.1016/j.cca.2020.07.020 -
The Cochrane Database of Systematic... May 2023Osteoporosis is characterized by low bone mass and micro-architectural deterioration of bone tissue leading to increased bone fragility. In people with... (Review)
Review
BACKGROUND
Osteoporosis is characterized by low bone mass and micro-architectural deterioration of bone tissue leading to increased bone fragility. In people with beta-thalassaemia, osteoporosis represents an important cause of morbidity and is due to a number of factors. First, ineffective erythropoiesis causes bone marrow expansion, leading to reduced trabecular bone tissue with cortical thinning. Second, excessive iron loading causes endocrine dysfunction, leading to increased bone turnover. Lastly, disease complications can result in physical inactivity, with a subsequent reduction in optimal bone mineralization. Treatments for osteoporosis in people with beta-thalassaemia include bisphosphonates (e.g. clodronate, pamidronate, alendronate; with or without hormone replacement therapy (HRT)), calcitonin, calcium, zinc supplementation, hydroxyurea, and HRT alone (for preventing hypogonadism). Denosumab, a fully human monoclonal antibody, inhibits bone resorption and increases bone mineral density (BMD). Finally, strontium ranelate simultaneously promotes bone formation and inhibits bone resorption, thus contributing to a net gain in BMD, increased bone strength, and reduced fracture risk. This is an update of a previously published Cochrane Review.
OBJECTIVES
To review the evidence on the efficacy and safety of treatment for osteoporosis in people with beta-thalassaemia.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, which includes references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched online trial registries. Date of most recent search: 4 August 2022.
SELECTION CRITERIA
Randomized controlled trials (RCTs) in people with beta-thalassaemia with: a BMD Z score below -2 standard deviations (SDs) for children aged under 15 years, adult males (aged 15 to 50 years) and premenopausal females aged over 15 years; or a BMD T score below -2.5 SDs for postmenopausal females and males aged over 50 years.
DATA COLLECTION AND ANALYSIS
Two review authors assessed the eligibility and risk of bias of the included RCTs, and extracted and analysed data. We assessed the certainty of the evidence using GRADE.
MAIN RESULTS
We included six RCTs (298 participants). Active interventions included bisphosphonates (3 trials, 169 participants), zinc supplementation (1 trial, 42 participants), denosumab (1 trial, 63 participants), and strontium ranelate (1 trial, 24 participants). The certainty of the evidence ranged from moderate to very low and was downgraded mainly due to concerns surrounding imprecision (low participant numbers), but also risk of bias issues related to randomization, allocation concealment, and blinding. Bisphosphonates versus placebo or no treatment Two RCTs compared bisphosphonates to placebo or no treatment. After two years, one trial (25 participants) found that alendronate and clodronate may increase BMD Z score compared to placebo at the femoral neck (mean difference (MD) 0.40, 95% confidence interval (CI) 0.22 to 0.58) and the lumbar spine (MD 0.14, 95% CI 0.05 to 0.23). One trial (118 participants) reported that neridronate compared to no treatment may increase BMD at the lumbar spine and total hip at six and 12 months; for the femoral neck, the study found increased BMD in the neridronate group at 12 months only. All results were of very low-certainty. There were no major adverse effects of treatment. Participants in the neridronate group reported less back pain; we considered this representative of improved quality of life (QoL), though the certainty of the evidence was very low. One participant in the neridronate trial (116 participants) sustained multiple fractures as a result of a traffic accident. No trials reported BMD at the wrist or mobility. Different doses of bisphosphonate compared One 12-month trial (26 participants) assessed different doses of pamidronate (60 mg versus 30 mg) and found a difference in BMD Z score favouring the 60 mg dose at the lumbar spine (MD 0.43, 95% CI 0.10 to 0.76) and forearm (MD 0.87, 95% CI 0.23 to 1.51), but no difference at the femoral neck (very low-certainty evidence). This trial did not report fracture incidence, mobility, QoL, or adverse effects of treatment. Zinc versus placebo One trial (42 participants) showed zinc supplementation probably increased BMD Z score compared to placebo at the lumbar spine after 12 months (MD 0.15, 95% CI 0.10 to 0.20; 37 participants) and 18 months (MD 0.34, 95% CI 0.28 to 0.40; 32 participants); the same was true for BMD at the hip after 12 months (MD 0.15, 95% CI 0.11 to 0.19; 37 participants) and 18 months (MD 0.26, 95% CI 0.21 to 0.31; 32 participants). The evidence for these results was of moderate certainty. The trial did not report BMD at the wrist, fracture incidence, mobility, QoL, or adverse effects of treatment. Denosumab versus placebo Based on one trial (63 participants), we are unsure about the effect of denosumab on BMD Z score at the lumbar spine, femoral neck, and wrist joint after 12 months compared to placebo (low-certainty evidence). This trial did not report fracture incidence, mobility, QoL, or adverse effects of treatment, but the investigators reported a reduction in bone pain measured on a visual analogue scale in the denosumab group after 12 months of treatment compared to placebo (MD -2.40 cm, 95% CI -3.80 to -1.00). Strontium ranelate One trial (24 participants) only narratively reported an increase in BMD Z score at the lumbar spine in the intervention group and no corresponding change in the control group (very low-certainty evidence). This trial also found a reduction in back pain measured on a visual analogue scale after 24 months in the strontium ranelate group compared to the placebo group (MD -0.70 cm (95% CI -1.30 to -0.10); we considered this measure representative of improved quality of life.
AUTHORS' CONCLUSIONS
Bisphosphonates may increase BMD at the femoral neck, lumbar spine, and forearm compared to placebo after two years' therapy. Zinc supplementation probably increases BMD at the lumbar spine and hip after 12 months. Denosumab may make little or no difference to BMD, and we are uncertain about the effect of strontium on BMD. We recommend further long-term RCTs on different bisphosphonates and zinc supplementation therapies in people with beta-thalassaemia-associated osteoporosis.
Topics: Adult; Child; Female; Male; Humans; Middle Aged; beta-Thalassemia; Alendronate; Pamidronate; Clodronic Acid; Denosumab; Osteoporosis; Diphosphonates; Fractures, Bone
PubMed: 37159055
DOI: 10.1002/14651858.CD010429.pub3