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Medicine Jun 2023Correction of calcium, phosphorus, and parathyroid hormone disorders is the standard of treatment in nondialysis patients with chronic kidney disease-mineral and bone... (Meta-Analysis)
Meta-Analysis
A meta-analysis of randomized controlled trials of tonifying kidney and strengthen bone therapy on nondialysis patients with chronic kidney disease-mineral and bone disorder.
BACKGROUND
Correction of calcium, phosphorus, and parathyroid hormone disorders is the standard of treatment in nondialysis patients with chronic kidney disease-mineral and bone disorder (CKD-MBD). However, the side effects and adverse reactions are still the main problems. Moreover, the lack of protection of kidney function in the treatment dramatically affects patients' health. Although Traditional Chinese Medicine, specifically tonifying kidney and strengthen bone (TKSB) therapy, is wildly applied to patients with CKD-MBD in China, the evidence of TKSB therapy in the treatment of CKD-MBD is limited. Thus, we conducted this meta-analysis to evaluate the efficacy and safety of TKSB therapy combined with Western medicine (WM) for nondialysis patients with CKD-MBD.
METHODS
Two investigators conducted systematic research of randomized controlled trials of TKSB therapy for CKD-MBD from 7 electronic databases. Methodological quality evaluations were performed using the Cochrane collaboration tool, and data analysis was conducted by RevMan v5.3 software and STATA v15.0.
RESULTS
In total, 8 randomized controlled trials involving 310 patients met the criteria of meta-analysis. The complete results showed that compared with WM alone, TKSB treatment could improve the clinical efficacy rate (risk ratio = 4.49, 95% confidence interval [CI]: [2.64, 7.61], P .00001), calcium (weighted mean difference [WMD] = 0.11, 95% CI: [0.08, 0.14], P < .00001), serum creatinine (WMD = 45.58, 95% CI: [32.35, 58.8], P < .00001) phosphorus (WMD = 0.11, 95% CI: [0.08, 0.13], P < .00001), parathyroid hormone (WMD = 16.72, 95% CI: [12.89, 20.55], P < .00001), blood urea nitrogen levels (WMD = 0.95, 95% CI: [0.26, 1.64], P = .007) on nondialysis patients with CKD-MBD, which was beneficial to improve the patients' bone metabolic state and renal function. In addition, evidence shows that, compared with WM alone, TKSB treatment is safe and does not increase side effects.
CONCLUSION
The systematic review found that TKSB therapy combined with WM has a positive effect on improving renal function and correcting bone metabolism disorder in nondialysis patients with CKD-MBD, which shows that Traditional Chinese Medicine is effective and safe in treating CKD-MBD. However, more high-quality, large-sample, multicenter clinical trials should be conducted to assess the safety and efficacy of TKSB therapy in treating nondialysis patients with CKD-MBD.Systematic review registration: INPLASY2020120086.
Topics: Humans; Calcium; Calcium, Dietary; Chronic Kidney Disease-Mineral and Bone Disorder; Drug-Related Side Effects and Adverse Reactions; Kidney; Multicenter Studies as Topic; Parathyroid Hormone; Randomized Controlled Trials as Topic
PubMed: 37352066
DOI: 10.1097/MD.0000000000034044 -
Journal of Orthopaedic Surgery and... Jun 2023Continuous use of glucocorticoids (GCs) has become the primary cause of secondary osteoporosis. Bisphosphonate drugs were given priority over denosumab and teriparatide... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Continuous use of glucocorticoids (GCs) has become the primary cause of secondary osteoporosis. Bisphosphonate drugs were given priority over denosumab and teriparatide in the 2017 American College of Rheumatology (ACR) guidelines but have a series of shortcomings. This study aims to explore the efficacy and safety of teriparatide and denosumab compared with those of oral bisphosphonate drugs.
METHODS
We systematically searched studies included in the PubMed, Web of Science, Embase, and Cochrane library databases and included randomized controlled trials that compared denosumab or teriparatide with oral bisphosphonates. Risk estimates were pooled using both fixed and random effects models.
RESULTS
We included 10 studies involving 2923 patients who received GCs for meta-analysis, including two drug base analyses and four sensitivity analyses. Teriparatide and denosumab were superior to bisphosphonates in increasing the bone mineral density (BMD) of the lumbar vertebrae [teriparatide: mean difference [MD] 3.98%, 95% confidence interval [CI] 3.61-4.175%, P = 0.00001; denosumab: MD 2.07%, 95% CI 0.97-3.17%, P = 0.0002]. Teriparatide was superior to bisphosphonates in preventing vertebral fractures and increasing hip BMD [MD 2.39%, 95% CI 1.47-3.32, P < 0.00001]. There was no statistically significant difference between serious adverse events, adverse events, and nonvertebral fracture prevention drugs.
CONCLUSIONS
Teriparatide and denosumab exhibited similar or even superior characteristics to bisphosphonates in our study, and we believe that they have the potential to become first-line GC-induced osteoporosis treatments, especially for patients who have previously received other anti-osteoporotic drugs with poor efficacy.
Topics: Humans; Teriparatide; Glucocorticoids; Denosumab; Bone Density Conservation Agents; Osteoporosis; Diphosphonates; Bone Density; Treatment Outcome
PubMed: 37349750
DOI: 10.1186/s13018-023-03920-4 -
Hemodialysis International.... Oct 2023The effects of denosumab on bone mineral density (BMD) and metabolism in patients with end-stage renal disease (ESRD) remain controversial. Hence, we performed a... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The effects of denosumab on bone mineral density (BMD) and metabolism in patients with end-stage renal disease (ESRD) remain controversial. Hence, we performed a systematic review and meta-analysis of observational studies.
METHODS
The MEDLINE, EMBASE, and Cochrane Library databases were searched in June 2022 to identify studies that evaluated the risk of denosumab-associated hypocalcemia and changes in bone metabolism, changes in BMD from baseline to post-treatment in patients with ESRD.
FINDINGS
Twelve studies with 348 participants were included. The pooled incidence of hypocalcemia during denosumab treatment was 35.0% (95% confidence interval [CI], 25%-46%; I = 63.6%). There were no significant changes in either the serum calcium or phosphate levels from the baseline to post-treatment period; the mean differences were 0.04 mg/dL (95% CI, -0.12 to 0.20 mg/dL) and -0.39 mg/dL (95% CI, -0.89 to 0.12 mg/dL). We found significant changes in the alkaline phosphatase and parathyroid hormone levels; the standardized mean differences were -2.98 (95% CI, -5.36 to -0.59) and -3.12 (95% CI: -4.94 to -1.29), respectively. Denosumab may increase BMD, with mean differences of 9.10% (95% CI: 4.07%-14.13%) and 9.00% (95% CI: 5.93%-12.07%) for the femoral neck and lumbar spine, respectively.
DISCUSSION
Denosumab increased the BMDs of the lumbar spine and femoral neck in patients with ESRD. The onset of hypocalcemia must be carefully monitored during denosumab administration.
Topics: Humans; Bone Density; Denosumab; Hypocalcemia; Bone Density Conservation Agents; Renal Dialysis; Kidney Failure, Chronic
PubMed: 37264758
DOI: 10.1111/hdi.13098 -
The Journal of Clinical Endocrinology... Oct 2023Secondary hyperparathyroidism (SHPT) is a complication of chronic kidney disease (CKD) affecting mineral and bone metabolism and characterized by excessive parathyroid... (Meta-Analysis)
Meta-Analysis
CONTEXT
Secondary hyperparathyroidism (SHPT) is a complication of chronic kidney disease (CKD) affecting mineral and bone metabolism and characterized by excessive parathyroid hormone (PTH) production and parathyroid hyperplasia.
OBJECTIVE
The objective of this analysis was to compare the efficacy and adverse effects of extended-release calcifediol (ERC) and paricalcitol (PCT) by assessing their effect on the biomarkers PTH, calcium, and phosphate in patients with non-dialysis CKD (ND-CKD).
METHODS
A systematic literature research was performed in PubMed to identify randomized control trials (RCTs). Quality assessment was done with the GRADE method. The effects of ERC vs PCT were compared using random effects in a frequentist setting.
RESULTS
Nine RCTs comprising 1426 patients were included in the analyses. The analyses were performed on 2 overlapping networks, due to nonreporting of outcomes in some of the included studies. No head-to-head trials were identified. No statistically significant differences in PTH reduction were found between PCT and ERC. Treatment with PCT showed statistically significant increases in calcium compared with ERC (0.2 mg/dL increase; 95% CI, -0.37 to -0.05 mg/dL). No differences in effects on phosphate were observed.
CONCLUSION
This network meta-analysis showed that ERC is comparable in lowering PTH levels vs PCT. ERC displayed avoidance of potentially clinically relevant increases in serum calcium, offering an effective and well-tolerated treatment option for the management of SHPT in patients with ND-CKD.
Topics: Humans; Calcifediol; Calcium; Ergocalciferols; Hyperparathyroidism, Secondary; Network Meta-Analysis; Parathyroid Hormone; Phosphates; Renal Insufficiency, Chronic; Randomized Controlled Trials as Topic
PubMed: 37235771
DOI: 10.1210/clinem/dgad289 -
Cureus Apr 2023Fracture nonunion remains a great challenge for orthopedic surgeons. Some bone fractures don't heal promptly, resulting in delayed unions and nonunions, and there is a... (Review)
Review
Fracture nonunion remains a great challenge for orthopedic surgeons. Some bone fractures don't heal promptly, resulting in delayed unions and nonunions, and there is a need for an additional surgical procedure. Previous research has shown that teriparatide, a type of synthetic parathyroid hormone, can promote the formation of callus and lead to healing in individuals with delayed or non-healing bone fractures. Limited systematic reviews exist that examine the use of teriparatide in cases of delayed healing or non-healing bone fractures, which have their limitations. In this review, we overcome those limitations by including prospective studies, retrospective studies, case reports, and case series together. A systematic search of the literature was conducted in both PubMed and Google Scholar up to September of the year 2022. The studies included in our research included adult patients (over the age of 16) diagnosed with delayed union or nonunion of any bone in the body (flat bone, long bone, short bone, or irregular bone). The studies were limited to those written in English. The outcomes that were tracked and recorded include the healing of the fracture and any negative side effects or adverse events. The initial search yielded 504 abstracts and titles. After reviewing these, 32 articles were selected for further analysis, which included 19 case reports, five case series, two retrospective studies, and six prospective studies. Studies included daily (20 micrograms) or weekly (56.5 micrograms) subcutaneous administration of teriparatide. The duration of follow-up for these studies varied from three to 24 months. Based on the available research, it appears that administering teriparatide subcutaneously is a safe treatment option for delayed healing and non-healing bone fractures, with very few to no reported negative side effects. Using teriparatide for induction of callus formation and treating delayed and nonunions is highly safe and effective.
PubMed: 37187628
DOI: 10.7759/cureus.37478 -
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 Renal Nutrition : the... Nov 2023Plant-based protein is of growing interest for dietary management of chronic kidney disease (CKD) and is hypothesized to preserve kidney function and reduce CKD-mineral...
INTRODUCTION
Plant-based protein is of growing interest for dietary management of chronic kidney disease (CKD) and is hypothesized to preserve kidney function and reduce CKD-mineral bone disorder (MBD) complications, among other benefits. This systematic review aimed to summarize the available clinical trial evidence for the effect of plant-based protein on kidney function and CKD-MBD outcomes in adults with stage 3-5 CKD not on dialysis.
METHODS
Searches of Medline, Embase, Agricola, CAB abstracts, Web of Science, Scopus, and hand searching were performed. Clinical trials with ≥8 participants ≥18 years of age with an estimated glomerular filtration rate <60 mL/min/1.73 m but not on dialysis were included. Additionally, only clinical trials with ≥1-week interventions with ≥50% dietary protein from plant-based sources and reported at least one outcome for both kidney function and CKD-MBD outcomes were included. Of the 10,962 identified abstracts, 32 met inclusion criteria and were assessed for risk of bias.
RESULTS
Results for kidney function and CKD-MBD outcomes were heterogenous, with most studies having suboptimal methodological quality. In most of the studies (27/32), protein source was altered only secondarily to low-protein diet interventions. Thus, data synthesis and interpretation were focused on a subset of five studies that investigated a change in protein source only (i.e., animal vs. plant). Of this subset, four studies reported no change in kidney function, while one study reported a decrease. Three studies reported no change in serum phosphorus, and one study reported lower serum phosphorus following a vegetarian diet. Further, limited data and inconclusive results were observed for phosphaturic hormones, parathyroid hormone, and fibroblast growth factor-23.
CONCLUSION
Current clinical trial evidence on plant-based protein interventions for preserving kidney function and preventing CKD-MBD is limited to inform clinical guidelines at this time. This systematic review emphasizes the ongoing need to research the effects of plant-based protein on kidney function and CKD-MBD outcomes.
Topics: Adult; Humans; Chronic Kidney Disease-Mineral and Bone Disorder; Plant Proteins; Kidney Failure, Chronic; Renal Insufficiency, Chronic; Parathyroid Hormone; Minerals; Phosphorus; Dietary Proteins; Kidney
PubMed: 37116624
DOI: 10.1053/j.jrn.2023.04.004 -
American Journal of Surgery Aug 2023We aim to evaluate the body of evidence reporting on normohormonal primary hyperparathyroidism (NHpHPT) patients to help guide their diagnosis, characterization and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
We aim to evaluate the body of evidence reporting on normohormonal primary hyperparathyroidism (NHpHPT) patients to help guide their diagnosis, characterization and treatment.
BACKGROUND
Normohormonal primary hyperparathyroidism is a term used to describe patients with a normal PTH and elevated calcium levels. There is limited understanding regarding the presentation and appropriate management of these patients.
METHODS
A systematic review was conducted: abstract and full-text screening were independently conducted by 2 investigators. Odds ratios (OR), standard mean differences (SMD) and 95% confidence intervals were calculated.
RESULTS
Twenty-two studies were identified. Patients with NHpHPT were more likely to present with lower PTH (p < 0.00001) and calcium (p < 0.00001) levels. Intraoperatively, the NHpHPT group was 1.8 times more likely to undergo bilateral neck exploration (BNE) and harbor multigland disease. The rates of surgical cure were 93% in the NHpHPT and 96% in the pHPT groups (p = 0.0003).
CONCLUSION
Symptomatic patients with NHpHPT benefit from parathyroidectomy with prolonged intraoperative PTH monitoring, and a low threshold for conversion to BNE.
Topics: Humans; Calcium; Parathyroid Hormone; Hyperparathyroidism, Primary; Retrospective Studies; Parathyroidectomy
PubMed: 37100740
DOI: 10.1016/j.amjsurg.2023.04.004 -
Osteoporosis International : a Journal... Aug 2023This meta-analysis demonstrated that a greater prevalence of delayed union and nonunion and a longer time to fracture healing in the group that did not receive TPTD... (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
This meta-analysis demonstrated that a greater prevalence of delayed union and nonunion and a longer time to fracture healing in the group that did not receive TPTD treatment after AFFs than in the group that received TPTD treatment.
PURPOSE
To date, there is no hard evidence for medical management after atypical femoral fracture (AFF), even though weak data indicate faster healing with teriparatide (TPTD). Herein, we aimed to investigate the effect of postfracture TPTD treatment on AFF healing using a pairwise meta-analysis focusing on delayed union, nonunion, and fracture healing time.
METHODS
A systematic search of the MEDLINE (PUBMED), Embase, and Cochrane Library databases was performed for studies investigating the effect of TPTD after AFF up to October 11, 2022. We compared the incidence of delayed union and nonunion and the time of fracture healing between the TPTD ( +) and TPTD (-) groups.
RESULTS
The 6 studies analyzed a total of 214 AFF patients, including 93 who received TPTD therapy after AFF and 121 who did not. The pooled analysis showed a significantly higher rate of delayed union in the TPTD (-) group than in the TPTD ( +) group (OR, 0.24; 95% CI, 0.11-0.52; P < 0.01; I = 0%), and a higher nonunion rate was observed in the TPTD (-) group than in the TPTD ( +) group with low heterogeneity (OR, 0.21; 95% CI, 0.06-0.78; P = 0.02; I = 0%). The TPTD (-) group required 1.69 months longer to achieve fracture union than the TPTD ( +) group, with statistical significance (MD = - 1.69, 95% CI: - 2.44 to - 0.95, P < 0.01; I = 13%). Subgroup analysis for patients with complete AFF showed that the TPTD (-) group had a higher rate of delayed union with low heterogeneity (OR, 0.22; 95% CI, 0.10-0.51; P < 0.01; I = 0%), but there was no significant difference in the nonunion rate between TPTD ( +) and TPTD (-) groups (OR, 0.35; 95% CI, 0.06-2.21; P = 0.25; I = 0%). Fracture healing took significantly longer in the TPTD (-) group (MD = - 1.81, 95% CI: - 2.55 to - 1.08; P < 0.01; I = 48%). The reoperation rate showed no significant difference between the two groups (OR, 0.29; 95% CI, 0.07-1.20; P = 0.09; I = 0%).
CONCLUSIONS
The current meta-analysis supported the hypothesis that TPTD treatment following AFF might benefit fracture healing, lowering the rate of delayed union and nonunion and shortening the fracture healing time.
Topics: Humans; Teriparatide; Fracture Healing; Bone Density Conservation Agents; Femoral Fractures
PubMed: 37095179
DOI: 10.1007/s00198-023-06768-w -
Therapeutic strategy for atypical ulnar fracture in long use of bisphosphonate: A systematic review.Journal of Orthopaedic Science :... May 2024Atypical fractures are caused by the combined effects of severe suppression of bone metabolism (SSBT) due to long-term bisphosphonate therapy and chronic repetitive bone...
BACKGROUND
Atypical fractures are caused by the combined effects of severe suppression of bone metabolism (SSBT) due to long-term bisphosphonate therapy and chronic repetitive bone microdamage. Atypical ulnar fractures (AUFs) due to SSBT are rare, and there is no standard treatment strategy for such fractures. The relevant literature was reviewed, and the treatment strategy for AUF is discussed.
METHODS
A systematic review was conducted. All studies on ulnar fractures in individuals with a history of bisphosphonate use were included, and the data were extracted and analyzed from the perspective of the therapeutic strategy.
RESULTS
Forty limbs of 35 patients were included. As for the treatment of AUF, 31 limbs were treated surgically, and conservative treatment with casting was performed for 9 limbs. The bone fusion rate was 22/40 (55.0%), and non-union was seen in all patients treated conservatively. There was a significant difference in the bone fusion rate between patients with surgical treatment and those with conservative treatment. The bone fusion rate of patients with parathyroid hormone (PTH) and surgery was 82.3% (14/17 limbs); the bone fusion rate with PTH and bone graft was 69.2% (9/13 limbs). However, there were no significant differences in the fusion rate in the groups with or without PTH, with or without bone grafting, or the combination of the two treatments. There was also no significant difference in the bone fusion rate in the groups with or without low-intensity pulsed ultrasound (LIPUS) treatment.
CONCLUSIONS
Based on the literature review, surgery is necessary to achieve bone union, but surgery alone is not adequate to achieve bony union. Bone grafting and the administration of PTH and LIPUS may promote early bone fusion, but the present study did not show significant advantages of these additional treatments for bone union.
Topics: Humans; Diphosphonates; Ulna Fractures; Bone Density Conservation Agents; Female; Male; Conservative Treatment
PubMed: 37032267
DOI: 10.1016/j.jos.2023.03.009