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BMJ (Clinical Research Ed.) May 2023To review the comparative effectiveness of osteoporosis treatments, including the bone anabolic agents, abaloparatide and romosozumab, on reducing the risk of fractures... (Meta-Analysis)
Meta-Analysis
Fracture risk reduction and safety by osteoporosis treatment compared with placebo or active comparator in postmenopausal women: systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials.
OBJECTIVE
To review the comparative effectiveness of osteoporosis treatments, including the bone anabolic agents, abaloparatide and romosozumab, on reducing the risk of fractures in postmenopausal women, and to characterise the effect of antiosteoporosis drug treatments on the risk of fractures according to baseline risk factors.
DESIGN
Systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials.
DATA SOURCES
Medline, Embase, and Cochrane Library to identify randomised controlled trials published between 1 January 1996 and 24 November 2021 that examined the effect of bisphosphonates, denosumab, selective oestrogen receptor modulators, parathyroid hormone receptor agonists, and romosozumab compared with placebo or active comparator.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomised controlled trials that included non-Asian postmenopausal women with no restriction on age, when interventions looked at bone quality in a broad perspective. The primary outcome was clinical fractures. Secondary outcomes were vertebral, non-vertebral, hip, and major osteoporotic fractures, all cause mortality, adverse events, and serious cardiovascular adverse events.
RESULTS
The results were based on 69 trials (>80 000 patients). For clinical fractures, synthesis of the results showed a protective effect of bisphosphonates, parathyroid hormone receptor agonists, and romosozumab compared with placebo. Compared with parathyroid hormone receptor agonists, bisphosphonates were less effective in reducing clinical fractures (odds ratio 1.49, 95% confidence interval 1.12 to 2.00). Compared with parathyroid hormone receptor agonists and romosozumab, denosumab was less effective in reducing clinical fractures (odds ratio 1.85, 1.18 to 2.92 for denosumab parathyroid hormone receptor agonists and 1.56, 1.02 to 2.39 for denosumab romosozumab). An effect of all treatments on vertebral fractures compared with placebo was found. In the active treatment comparisons, denosumab, parathyroid hormone receptor agonists, and romosozumab were more effective than oral bisphosphonates in preventing vertebral fractures. The effect of all treatments was unaffected by baseline risk indicators, except for antiresorptive treatments that showed a greater reduction of clinical fractures compared with placebo with increasing mean age (number of studies=17; β=0.98, 95% confidence interval 0.96 to 0.99). No harm outcomes were seen. The certainty in the effect estimates was moderate to low for all individual outcomes, mainly because of limitations in reporting, nominally indicating a serious risk of bias and imprecision.
CONCLUSIONS
The evidence indicated a benefit of a range of treatments for osteoporosis in postmenopausal women for clinical and vertebral fractures. Bone anabolic treatments were more effective than bisphosphonates in the prevention of clinical and vertebral fractures, irrespective of baseline risk indicators. Hence this analysis provided no clinical evidence for restricting the use of anabolic treatment to patients with a very high risk of fractures.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42019128391.
Topics: Humans; Female; Bone Density Conservation Agents; Network Meta-Analysis; Postmenopause; Denosumab; Receptor, Parathyroid Hormone, Type 1; Osteoporosis; Osteoporotic Fractures; Diphosphonates; Spinal Fractures; Risk Reduction Behavior; Osteoporosis, Postmenopausal; Randomized Controlled Trials as Topic
PubMed: 37130601
DOI: 10.1136/bmj-2021-068033 -
Journal of Bone and Mineral Research :... Nov 2022The last international guidelines on the evaluation and management of primary hyperparathyroidism (PHPT) were published in 2014. Research since that time has led to new... (Review)
Review
The last international guidelines on the evaluation and management of primary hyperparathyroidism (PHPT) were published in 2014. Research since that time has led to new insights into epidemiology, pathophysiology, diagnosis, measurements, genetics, outcomes, presentations, new imaging modalities, target and other organ systems, pregnancy, evaluation, and management. Advances in all these areas are demonstrated by the reference list in which the majority of listings were published after the last set of guidelines. It was thus, timely to convene an international group of over 50 experts to review these advances in our knowledge. Four Task Forces considered: 1. Epidemiology, Pathophysiology, and Genetics; 2. Classical and Nonclassical Features; 3. Surgical Aspects; and 4. Management. For Task Force 4 on the Management of PHPT, Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology addressed surgical management of asymptomatic PHPT and non-surgical medical management of PHPT. The findings of this systematic review that applied GRADE methods to randomized trials are published as part of this series. Task Force 4 also reviewed a much larger body of new knowledge from observations studies that did not specifically fit the criteria of GRADE methodology. The full reports of these 4 Task Forces immediately follow this summary statement. Distilling the essence of all deliberations of all Task Force reports and Methodological reviews, we offer, in this summary statement, evidence-based recommendations and guidelines for the evaluation and management of PHPT. Different from the conclusions of the last workshop, these deliberations have led to revisions of renal guidelines and more evidence for the other recommendations. The accompanying papers present an in-depth discussion of topics summarized in this report. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Topics: Humans; Hyperparathyroidism, Primary
PubMed: 36245251
DOI: 10.1002/jbmr.4677 -
Endocrine-related Cancer Apr 2023Parathyroid carcinoma is one of the least common endocrine malignancies and accounts for approximately 1% of all patients with primary hyperparathyroidism. A systematic... (Review)
Review
Parathyroid carcinoma is one of the least common endocrine malignancies and accounts for approximately 1% of all patients with primary hyperparathyroidism. A systematic review of peer-reviewed literature published between January 2000 and March 2022 via Medline, Embase, Cochrane Central Register of Controlled Trials, EudraCT, ClinicalTrials.gov, CINAHL and SCOPUS was conducted. Manuscripts were eligible if they included data on adult non-pregnant populations with parathyroid carcinoma. No restrictions regarding interventions, comparators or duration of follow-up were imposed. Single case reports, reviews or meta-analyses were excluded. Outcomes of interest were molecular pathogenesis, clinical presentation, differential diagnosis, treatment, follow-up and overall survival. Study quality was evaluated using the Newcastle-Ottawa Scale for observational studies. This review included 75 studies from 17 countries, reporting on more than 3000 patients with parathyroid carcinoma. CDC73 mutation has been recognised as playing a pivotal role in molecular pathogenesis. Parathyroid carcinoma typically presents with markedly increased calcium and parathyroid hormone levels. The most frequently described symptoms were bone and muscle pain or weakness. En bloc resection remains the gold standard for the surgical approach. The 5-year overall survival ranged from 60 to 93%, with resistant hypercalcaemia a significant cause of mortality. Emerging evidence indicating that targeted therapy, based on molecular biomarkers, presents a novel treatment option. The rarity of PC and need for personalised treatment warrant multidisciplinary management in a 'centre of excellence' with a track record in PC management.
Topics: Adult; Humans; Parathyroid Neoplasms
PubMed: 36621911
DOI: 10.1530/ERC-22-0287 -
Journal of Renal Nutrition : the... Jan 2021Bone and mineral metabolism becomes dysregulated with progression of chronic kidney disease (CKD), and increasing levels of parathyroid hormone serve as an adaptive...
Bone and mineral metabolism becomes dysregulated with progression of chronic kidney disease (CKD), and increasing levels of parathyroid hormone serve as an adaptive response to maintain normal phosphorus and calcium levels. In end-stage renal disease, this response becomes maladaptive and high levels of phosphorus may occur. We summarize strategies to control hyperphosphatemia based on a systematic literature review of clinical trial and real-world observational data on phosphorus control in hemodialysis patients with CKD-mineral bone disorder (CKD-MBD). These studies suggest that current management options (diet and lifestyle changes; regular dialysis treatment; and use of phosphate binders, vitamin D, calcimimetics) have their own benefits and limitations with variable clinical outcomes. A more integrated approach to phosphorus control in dialysis patients may be necessary, incorporating measurement of multiple biomarkers of CKD-MBD pathophysiology (calcium, phosphorus, and parathyroid hormone) and correlation between diet adjustments and CKD-MBD drugs, which may facilitate improved patient management.
Topics: Calcimimetic Agents; Chelating Agents; Diet; Humans; Hyperphosphatemia; Kidney Failure, Chronic; Vitamin D
PubMed: 32386937
DOI: 10.1053/j.jrn.2020.02.003 -
Translational Psychiatry Oct 2021Postpartum depression (PPD) is the most common psychological condition following childbirth, and may have a detrimental effect on the social and cognitive health of...
Postpartum depression (PPD) is the most common psychological condition following childbirth, and may have a detrimental effect on the social and cognitive health of spouses, infants, and children. The aim of this study was to complete a comprehensive overview of the current literature on the global epidemiology of PPD. A total of 565 studies from 80 different countries or regions were included in the final analysis. Postpartum depression was found in 17.22% (95% CI 16.00-18.51) of the world's population. Meta-regression analysis showed that study size, country or region development, and country or region income were the causes of heterogeneity. Multivariable meta-regression analysis found that study size and country or area development were the most important predictors. Varied prevalence rates were noted in geographic regions with the highest rate found in Southern Africa (39.96%). Of interested was a significantly lower rate of PPD in developed countries or high-income countries or areas. Furthermore, the findings showed that there was a substantial difference in rates of PPD when marital status, educational level, social support, spouse care, violence, gestational age, breast feeding, child mortality, pregnancy plan, financial difficulties, partnership, life stress, smoking, alcohol intake, and living conditions were considered in the pooled estimates. Our results indicated that one out of every five women experiences PPD which is linked to income and geographic development. It is triggered by a variety of causes that necessitate the attention and committed intervention of primary care providers, clinicians, health authorities, and the general population.
Topics: Child; Depression; Depression, Postpartum; Female; Humans; Infant; Postpartum Period; Pregnancy; Prevalence; Social Support
PubMed: 34671011
DOI: 10.1038/s41398-021-01663-6 -
International Journal of Molecular... Sep 2020Chronic kidney disease (CKD) is associated with the development of mineral bone disorder (MBD), osteoporosis, and fragility fractures. Among CKD patients, adynamic bone...
Chronic kidney disease (CKD) is associated with the development of mineral bone disorder (MBD), osteoporosis, and fragility fractures. Among CKD patients, adynamic bone disease or low bone turnover is the most common type of renal osteodystrophy. The consequences of CKD-MBD include increased fracture risk, greater morbidity, and mortality. Thus, the goal is to prevent the occurrences of fractures by means of alleviating CKD-induced MBD and treating subsequent osteoporosis. Changes in mineral and humoral metabolism as well as bone structure develop early in the course of CKD. CKD-MBD includes abnormalities of calcium, phosphorus, PTH, and/or vitamin D; abnormalities in bone turnover, mineralization, volume, linear growth, or strength; and/or vascular or other soft tissue calcification. In patients with CKD-MBD, using either DXA or FRAX to screen fracture risk should be considered. Biomarkers such as bALP and iPTH may assist to assess bone turnover. Before initiating an antiresorptive or anabolic agent to treat osteoporosis in CKD patients, lifestyle modifications, such as exercise, calcium, and vitamin D supplementation, smoking cessation, and avoidance of excessive alcohol intake are important. Managing hyperphosphatemia and SHPT are also crucial. Understanding the complex pathogenesis of CKD-MBD is crucial in improving one's short- and long-term outcomes. Treatment strategies for CKD-associated osteoporosis should be patient-centered to determine the type of renal osteodystrophy. This review focuses on the mechanism, evaluation and management of patients with CKD-MBD. However, further studies are needed to explore more details regarding the underlying pathophysiology and to assess the safety and efficacy of agents for treating CKD-MBD.
Topics: Biomarkers; Bone and Bones; Calcium; Calcium, Dietary; Chronic Kidney Disease-Mineral and Bone Disorder; Fractures, Bone; Humans; Kidney Diseases; Osteoporosis; Phosphorus; Renal Dialysis; Renal Insufficiency, Chronic; Vitamin D
PubMed: 32961953
DOI: 10.3390/ijms21186846 -
American Journal of Kidney Diseases :... Nov 2023Vitamin D is widely used to manage chronic kidney disease-mineral and bone disorder (CKD-MBD). We evaluated the effects of vitamin D therapy on mortality,...
RATIONALE & OBJECTIVE
Vitamin D is widely used to manage chronic kidney disease-mineral and bone disorder (CKD-MBD). We evaluated the effects of vitamin D therapy on mortality, cardiovascular, bone, and kidney outcomes in adults with CKD.
STUDY DESIGN
Systematic review of randomized controlled trials (RCT) with highly sensitive searching of MEDLINE, Embase, and CENTRAL, through February 25, 2023.
SETTING & STUDY POPULATIONS
Adults with stage 3, 4, or 5 CKD, including kidney failure treated with dialysis. Recipients of a kidney transplant were excluded.
SELECTION CRITERIA FOR STUDIES
RCTs with≥3 months of follow-up evaluating a vitamin D compound.
DATA EXTRACTION
Data were extracted independently by three investigators.
ANALYTICAL APPROACH
Treatment estimates were summarized using random effects meta-analysis. Primary review endpoints were all-cause death, cardiovascular death, and fracture. Secondary outcomes were major adverse cardiovascular events, hospitalization, bone mineral density, parathyroidectomy, progression to kidney failure, proteinuria, estimated glomerular filtration rate, hypercalcemia, hyperphosphatemia, biochemical markers of CKD-MBD, and various intermediate outcome measures of cardiovascular disease. Risk of bias was assessed using the Cochrane Risk of Bias (RoB) 2 tool. Evidence certainty was adjudicated using GRADE.
RESULTS
Overall, 128 studies involving 11,270 participants were included. Compared with placebo, vitamin D therapy probably had no effect on all-cause death (relative risk [RR], 1.04; 95% CI, 0.84-1.24); and uncertain effects on fracture (RR, 0.68; 95% CI, 0.37-1.23) and cardiovascular death (RR, 0.73; 95% CI, 0.31-1.71). Compared with placebo, vitamin D therapy lowered serum parathyroid hormone and alkaline phosphatase, but increased serum calcium.
LIMITATIONS
Data were limited by trials with short-term follow-up periods, small sample size, and the suboptimal quality.
CONCLUSIONS
Vitamin D therapy did not reduce the risk of all-cause death in people with CKD. Effects on fracture and cardiovascular and kidney outcomes were uncertain.
TRIAL REGISTRATION
Registered at PROSPERO with study number CRD42017057691.
PLAIN-LANGUAGE SUMMARY
Chronic kidney disease (CKD) is associated with increased risk of death, cardiovascular disease, and fractures. This excess risk is thought to be related to changes in bone and mineral metabolism, leading to the development of CKD-mineral and bone disorder (CKD-MBD) which is characterized by vascular calcification and reduced bone quality. Vitamin D is commonly used in the treatment of this condition. We reviewed randomized controlled trials examining the effect of vitamin D therapy in CKD. We found that vitamin D therapy affects serum biomarkers, including an increase in serum calcium. However, it probably has no effect on risk of all-cause death in CKD, and the effects on other clinical bone, cardiovascular, and kidney outcomes are uncertain.
PubMed: 37356648
DOI: 10.1053/j.ajkd.2023.04.003 -
Genetics in Medicine : Official Journal... Mar 2023This review aimed to update the clinical practice guidelines for managing adults with 22q11.2 deletion syndrome (22q11.2DS). The 22q11.2 Society recruited expert...
This review aimed to update the clinical practice guidelines for managing adults with 22q11.2 deletion syndrome (22q11.2DS). The 22q11.2 Society recruited expert clinicians worldwide to revise the original clinical practice guidelines for adults in a stepwise process according to best practices: (1) a systematic literature search (1992-2021), (2) study selection and synthesis by clinical experts from 8 countries, covering 24 subspecialties, and (3) formulation of consensus recommendations based on the literature and further shaped by patient advocate survey results. Of 2441 22q11.2DS-relevant publications initially identified, 2344 received full-text review, with 2318 meeting inclusion criteria (clinical care relevance to 22q11.2DS) including 894 with potential relevance to adults. The evidence base remains limited. Thus multidisciplinary recommendations represent statements of current best practice for this evolving field, informed by the available literature. These recommendations provide guidance for the recognition, evaluation, surveillance, and management of the many emerging and chronic 22q11.2DS-associated multisystem morbidities relevant to adults. The recommendations also address key genetic counseling and psychosocial considerations for the increasing numbers of adults with this complex condition.
Topics: Adult; Humans; Clinical Relevance; Consensus; DiGeorge Syndrome; Genetic Counseling; Surveys and Questionnaires
PubMed: 36729052
DOI: 10.1016/j.gim.2022.11.012 -
EBioMedicine Feb 2022Calcium plays a role in a wide range of biological functions. Here we conducted a phenome-wide Mendelian randomisation (MR-PheWAS) analysis and a systematic review for...
BACKGROUND
Calcium plays a role in a wide range of biological functions. Here we conducted a phenome-wide Mendelian randomisation (MR-PheWAS) analysis and a systematic review for MR studies to comprehensively investigate the health effects of serum calcium.
METHODS
One-hundred and thirty genetic variants strongly associated with serum calcium levels were used as instrumental variables. A phenome-wide association analysis (PheWAS) was conducted to examine the associations of genetically predicted serum calcium with 1473 distinct phenotypes in the UK Biobank including 339,197 individuals. Observed associations in PheWAS were further tested for replication in two-sample MR replication analysis. A systematic review for MR studies on serum calcium was performed to synthesize the published evidence and compare with the current MR-PheWAS findings.
FINDINGS
Higher genetically predicted calcium levels were associated with decreased risk of 5 diseases in dermatologic and musculoskeletal systems and increased risk of 17 diseases in circulatory, digestive, endocrine, genitourinary and immune systems. Eight associations were replicated in two-sample MR analysis. These included decreased risk of osteoarthritis and increased risk of coronary artery disease, myocardial infarction, coronary atherosclerosis, hyperparathyroidism, disorder of parathyroid gland, gout, and calculus of kidney and ureter with increased serum calcium. Systematic review of 25 MR studies provided supporting evidence on five out of the eight disease outcomes, while the increased risk of gout, hyperparathyroidism and disorder of parathyroid gland were novel findings.
INTERPRETATION
This study found wide-ranged health effects of high serum calcium, which suggests that the benefits and adversities of strategies promoting calcium intake should be assessed.
FUNDING
ET is supported by a CRUK Career Development Fellowship (C31250/A22804). XL is supported by the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province. SCL acknowledges research funding from the Swedish Heart Lung Foundation (Hjärt-Lungfonden, 20210351), the Swedish Research Council (Vetenskapsrådet, 2019-00977), and the Swedish Cancer Society (Cancerfonden).
Topics: Calcium; Genome-Wide Association Study; Humans; Mendelian Randomization Analysis; Phenomics; Phenotype; Polymorphism, Single Nucleotide
PubMed: 35134646
DOI: 10.1016/j.ebiom.2022.103865 -
Medical Sciences (Basel, Switzerland) Mar 2022: To date, there is no satisfactory treatment for patients with calcium and vitamin D supplementation refractive hypoparathyroidism. Parathyroid allotransplantation by... (Review)
Review
: To date, there is no satisfactory treatment for patients with calcium and vitamin D supplementation refractive hypoparathyroidism. Parathyroid allotransplantation by design is a one-time cure through its restoration of the parathyroid function and, therefore, could be the solution. A systematic literature review is conducted in the present paper, with the aim of outlining the possibilities of parathyroid allotransplantation and to calculate its efficacy. Additionally, various transplantation characteristics are linked to success. This review is carried out according to the PRISMA statement and checklist. Relevant articles were searched for in medical databases with the most recent literature search performed on 9 December 2021. In total, 24 articles involving 22 unique patient cohorts were identified with 203 transplantations performed on 148 patients. Numerous types of (exploratory) interventions were carried out with virtually no protocols that were alike: there was the use of (non-) cryopreserved parathyroid tissue combined with direct transplantation or pretreatment using in vitro techniques, such as culturing cells and macro-/microencapsulation. The variability increased further when considering immunosuppression, graft histology, and donor-recipient compatibility, but this was found to be reported in its entirety by exception. As a result of the large heterogeneity among studies, we constructed our own criterium for transplantation success. With only the studies eligible for our assessment, the pooled success rate for parathyroid allotransplantation emerged to be 46% (13/28 transplantations) with a median follow-up duration of 12 months (Q1-Q3: 8-24 months). Manifold possibilities have been explored around parathyroid allotransplantation but are presented as a double-edged sword due to high clinical diverseness, low expertise in carrying out the procedure, and unsatisfactory study quality. Transplantations carried out with permanent immunosuppression seem to be the most promising, but, in its current state, little could be said about the treatment efficacy with a high quality of evidence. Of foremost importance in pursuing the answer whether parathyroid allotransplantation is a suitable treatment for hypoparathyroidism, a standardized definition of transplantation success must be established with a high-quality trial.
Topics: Humans; Hypoparathyroidism; Immunosuppression Therapy; Parathyroid Glands; Tissue Donors; Treatment Outcome
PubMed: 35323218
DOI: 10.3390/medsci10010019