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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 -
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 -
Medicine Mar 2023Glucocorticoid-induced osteoporosis (GIOP) is the most common secondary osteoporosis. Bushen Jiangu (BSJG), a classic traditional Chinese medicine (TCM) therapy, is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Glucocorticoid-induced osteoporosis (GIOP) is the most common secondary osteoporosis. Bushen Jiangu (BSJG), a classic traditional Chinese medicine (TCM) therapy, is widely used for treatment of GIOP. We conducted a meta-analysis to evaluate the effectiveness and safety of BSJG therapy on the treatment of GIOP.
METHODS
We searched randomized controlled trials (RCTs) of BSJG therapy for GIOP in 10 databases. Methodological quality assessment was performed by using the Cochrane collaboration tool. RevMan v5.3 and Stata v14.0 software were used for performing data analysis. This study was conducted and reported following the PRISMA checklist.
RESULTS
Overall, 14 RCTs with 988 participants met the inclusion criteria. Pooled results indicated that BSJG therapy contributed to a betterment in improving the clinical efficacy rate of GIOP (risk ratio [RR] = 1.22, 95% confidence interval [CI]: 1.14, 1.30, P < .00001). The pooled results also indicated that BSJG therapy increased lumbar spine bone mineral density (LS-BMD) (weighted mean difference [WMD] = 0.21, 95% CI: 0.08, 0.33, P = .001), total hip bone mineral density (TH-BMD) (WMD = 0.16, 95% CI: 0.09, 0.24, P < .0001), and femoral neck bone mineral density (FN-BMD) (WMD = 0.07, 95% CI: 0.03, 0.10, P = .0001). Furthermore, our results indicated that BSJG therapy improved visual analogue scale (VAS) score (WMD = -0.60, 95% CI: -0.97, -0.23, P = .002), parathyroid hormone (PTH) (standardized mean difference [SMD] = -0.93, 95% CI: -1.58, -0.27, P = .006), and N-terminal propeptide of type I precollagen (PINP) (SMD = 0.69, 95% CI: 0.44, 0.95, P < .00001). In terms of safety, there was no significant difference in the adverse events (AEs) between the 2 groups (RR = 1.45, 95% CI: 0.63, 3.31, P = .38).
CONCLUSION
Our analysis indicates that BSJG therapy has a valid and safe effect on the treatment of GIOP in the clinic. However, the results need to be confirmed in more well-designed and large-scale RCTs.
Topics: Humans; Glucocorticoids; Randomized Controlled Trials as Topic; Osteoporosis; Bone Density; Bone Density Conservation Agents
PubMed: 36930100
DOI: 10.1097/MD.0000000000033278 -
Endocrine Journal May 2023Few studies have considered the effect of statins on bone turnover biomarker levels and the results of these studies are inconsistent. Here we performed a meta-analysis... (Meta-Analysis)
Meta-Analysis
Few studies have considered the effect of statins on bone turnover biomarker levels and the results of these studies are inconsistent. Here we performed a meta-analysis of the effect of statins on bone turnover biomarker levels. We used keywords, free words, and related words that included the terms "hydroxymethylglutaryl-CoA reductase inhibitors," "statin," and "bone turnover biomarkers" to search PubMed, Cochrane Library, and Embase. The Cochrane Risk Bias Evaluation Tool was used to evaluate the risk of bias, and Review Manager 5.3 and Stata 13.0 were used for statistical analyses. Six randomized controlled trials involving a total of 382 subjects were included in the meta-analysis. The results showed that statins increased the osteocalcin (OC) [mean difference (MD) = 0.73 ng/mL, 95% CI: 0.12, 1.35, I = 23% and p = 0.26], and decreased cross-linked N-telopeptide (NTX) (MD = -1.14 nM BCE, 95% CI: -2.21, -0.07, I = 0%, p = 0.53) and C-terminal peptide of type I collagen (CTX) (MD = -0.03 ng/mL, 95% CI: -0.05, -0.01, I = 0% and p = 0.56). There was no effect on bone-specific alkaline phosphatase (MD = -1.37 U/L, 95% CI: -3.09, 0.34, I = 0% and p = 0.94) and intact parathyroid hormone (MD = -1.73 pg/mL, 95% CI: -4.35, 0.89, I = 0% and p = 0.77). Statins increase bone formation biomarker OC and decrease bone resorption biomarker NTX and CTX levels.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Randomized Controlled Trials as Topic; Bone Remodeling; Bone Resorption; Biomarkers
PubMed: 36928061
DOI: 10.1507/endocrj.EJ22-0512 -
The Journal of Clinical Endocrinology... Aug 2023Kenny-Caffey syndrome (KCS) is a rare hereditary disorder characterized by short stature, hypoparathyroidism, and electrolyte disturbances. KCS1 and KCS2 are caused by...
CONTEXT
Kenny-Caffey syndrome (KCS) is a rare hereditary disorder characterized by short stature, hypoparathyroidism, and electrolyte disturbances. KCS1 and KCS2 are caused by pathogenic variants in TBCE and FAM111A, respectively. Clinically the phenotypes are difficult to distinguish.
OBJECTIVE
The objective was to determine and expand the phenotypic spectrum of KCS1 and KCS2 in order to anticipate complications that may arise in these disorders.
METHODS
We clinically and genetically analyzed 10 KCS2 patients from 7 families. Because we found unusual phenotypes in our cohort, we performed a systematic review of genetically confirmed KCS cases using PubMed and Scopus. Evaluation by 3 researchers led to the inclusion of 26 papers for KCS1 and 16 for KCS2, totaling 205 patients. Data were extracted following the Cochrane guidelines and assessed by 2 independent researchers.
RESULTS
Several patients in our KCS2 cohort presented with intellectual disability (3/10) and chronic kidney disease (6/10), which are not considered common findings in KCS2. Systematic review of all reported KCS cases showed that the phenotypes of KCS1 and KCS2 overlap for postnatal growth retardation (KCS1: 52/52, KCS2: 23/23), low parathyroid hormone levels (121/121, 16/20), electrolyte disturbances (139/139, 24/27), dental abnormalities (47/50, 15/16), ocular abnormalities (57/60, 22/23), and seizures/spasms (103/115, 13/16). Symptoms more prevalent in KCS1 included intellectual disability (74/80, 5/24), whereas in KCS2 bone cortical thickening (1/18, 16/20) and medullary stenosis (7/46, 27/28) were more common.
CONCLUSION
Our case series established chronic kidney disease as a new feature of KCS2. In the literature, we found substantial overlap in the phenotypic spectra of KCS1 and KCS2, but identified intellectual disability and the abnormal bone phenotype as the most distinguishing features.
Topics: Humans; Intellectual Disability; Hyperostosis, Cortical, Congenital; Phenotype; Electrolytes; Hypoparathyroidism
PubMed: 36916904
DOI: 10.1210/clinem/dgad147 -
International Journal of Surgery... Mar 2023Routine prophylaxis for at-risk patients may reduce the occurrence of postoperative hypocalcemia but is not widely adopted due to a lack of evidence on the efficacy of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Routine prophylaxis for at-risk patients may reduce the occurrence of postoperative hypocalcemia but is not widely adopted due to a lack of evidence on the efficacy of available prophylactic strategies. In this study, we compared the relative efficacy of prophylactic strategies for postthyroidectomy hypocalcemia with a systematic review and network meta-analysis.
METHODS
PubMed, Embase, and Cochrane Library were searched, covering the period from 1980 to May 2022, for randomized controlled trials (RCTs) comparing calcium, vitamin D 3 , activated vitamin D 3 , teriparatide, steroids, and magnesium with placebo or each other in patients receiving total or completion thyroidectomy. Involved RCTs reporting symptomatic or biochemical hypocalcemia. The primary outcome was symptomatic hypocalcemia, defined as circumoral tingling, and Chvostek and Trousseau signs. The secondary outcome was biochemical hypocalcemia. Risk of bias was assessed using the Cochrane risk of bias assessment tool for randomized trials. Pooled estimates were calculated using a random-effects inverse-variance weighting model. The network meta-analysis was performed under the frequentist framework. This meta-analysis was registered on the PROSPERO (International prospective register of systematic reviews) (CRD42022299982).
RESULTS
Twenty-seven RCTs comprising 3382 patients are included. Prophylactic strategies of teriparatide, oral calcium plus vitamin D 3 , and oral calcium plus activated vitamin D 3 are superior to placebo in reducing symptomatic hypocalcemia. Teriparatide emerged as the most effective strategy for symptomatic hypocalcemia [relative risk (RR): 0.18; 95% CI: 0.03-0.98], followed by oral calcium plus activated vitamin D 3 (RR: 0.42; 95% CI: 0.25-0.73) and oral calcium plus vitamin D 3 (RR: 0.43; 95% CI: 0.26-0.71). Evidence on monotherapy with either oral calcium or vitamin D 3 in reducing symptomatic hypocalcemia is insufficient. Intravenous calcium and oral calcium are effective in reducing biochemical hypocalcemia.
CONCLUSIONS
This network meta-analysis provides information on the relative efficacy of current prophylactic strategies for postthyroidectomy hypocalcemia. Teriparatide performed better than other interventions and would seem appropriate for deployment among high-risk populations.
Topics: Humans; Calcium; Cholecalciferol; Hypocalcemia; Network Meta-Analysis; Teriparatide
PubMed: 36912560
DOI: 10.1097/JS9.0000000000000266 -
The Cochrane Database of Systematic... Mar 2023Primary hyperparathyroidism (PHPT), a disorder in which the parathyroid glands produce excessive amounts of parathyroid hormone, is most common in older adults and... (Review)
Review
BACKGROUND
Primary hyperparathyroidism (PHPT), a disorder in which the parathyroid glands produce excessive amounts of parathyroid hormone, is most common in older adults and postmenopausal women. While most people with PHPT are asymptomatic at diagnosis, symptomatic disease can lead to hypercalcaemia, osteoporosis, renal stones, cardiovascular abnormalities and reduced quality of life. Surgical removal of abnormal parathyroid tissue (parathyroidectomy) is the only established treatment for adults with symptomatic PHPT to prevent exacerbation of symptoms and to be cured of PHPT. However, the benefits and risks of parathyroidectomy compared to simple observation or medical therapy for asymptomatic and mild PHPT are not well established.
OBJECTIVES
To evaluate the benefits and harms of parathyroidectomy in adults with PHPT compared to simple observation or medical therapy.
SEARCH METHODS
We searched CENTRAL, MEDLINE, LILACS, ClinicalTrials.gov and WHO ICTRP from their date of inception until 26 November 2021. We applied no language restrictions.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing parathyroidectomy with simple observation or medical therapy for the treatment of adults with PHPT.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were 1. cure of PHPT, 2. morbidity related to PHPT and 3. serious adverse events. Our secondary outcomes were 1. all-cause mortality, 2. health-related quality of life and 3. hospitalisation for hypercalcaemia, acute renal impairment or pancreatitis. We used GRADE to assess the certainty of the evidence for each outcome.
MAIN RESULTS
We identified eight eligible RCTs that included 447 adults with (mostly asymptomatic) PHPT; 223 participants were randomised to parathyroidectomy. Follow-up duration varied from six months to 24 months. Of the 223 participants (37 men) randomised to surgery, 164 were included in the analyses, of whom 163 were cured at six to 24 months (overall cure rate 99%). Parathyroidectomy compared to observation probably results in a large increase in cure rate at six to 24 months follow-up: 163/164 participants (99.4%) in the parathyroidectomy group and 0/169 participants in the observation or medical therapy group were cured of their PHPT (8 studies, 333 participants; moderate certainty). No studies explicitly reported intervention effects on morbidities related to PHPT, such as osteoporosis, osteopenia, kidney dysfunction, urolithiasis, cognitive dysfunction or cardiovascular disease, although some studies reported surrogate outcomes for osteoporosis and cardiovascular disease. A post-hoc analysis revealed that parathyroidectomy, compared to observation or medical therapy, may have little or no effect after one to two years on bone mineral density (BMD) at the lumbar spine (mean difference (MD) 0.03 g/cm,95% CI -0.05 to 0.12; 5 studies, 287 participants; very low certainty). Similarly, compared to observation, parathyroidectomy may have little or no effect on femoral neck BMD after one to two years (MD -0.01 g/cm, 95% CI -0.13 to 0.11; 3 studies, 216 participants; very low certainty). However, the evidence is very uncertain for both BMD outcomes. Furthermore, the evidence is very uncertain about the effect of parathyroidectomy on improving left ventricular ejection fraction (MD -2.38%, 95% CI -4.77 to 0.01; 3 studies, 121 participants; very low certainty). Four studies reported serious adverse events. Three of these reported zero events in both the intervention and control groups; consequently, we were unable to include data from these three studies in the pooled analysis. The evidence suggests that parathyroidectomy compared to observation may have little or no effect on serious adverse events (RR 3.35, 95% CI 0.14 to 78.60; 4 studies, 168 participants; low certainty). Only two studies reported all-cause mortality. One study could not be included in the pooled analysis as zero events were observed in both the intervention and control groups. Parathyroidectomy compared to observation may have little or no effect on all-cause mortality, but the evidence is very uncertain (RR 2.11, 95% CI 0.20 to 22.60; 2 studies, 133 participants; very low certainty). Three studies measured health-related quality of life using the 36-Item Short Form Health Survey (SF-36) and reported inconsistent differences in scores for different domains of the questionnaire between parathyroidectomy and observation. Six studies reported hospitalisations for the correction of hypercalcaemia. Two studies reported zero events in both the intervention and control groups and could not be included in the pooled analysis. Parathyroidectomy, compared to observation, may have little or no effect on hospitalisation for hypercalcaemia (RR 0.91, 95% CI 0.20 to 4.25; 6 studies, 287 participants; low certainty). There were no reported hospitalisations for renal impairment or pancreatitis.
AUTHORS' CONCLUSIONS
In accordance with the literature, our review findings suggest that parathyroidectomy, compared to simple observation or medical (etidronate) therapy, probably results in a large increase in cure rates of PHPT (with normalisation of serum calcium and parathyroid hormone levels to laboratory reference values). Parathyroidectomy, compared with observation, may have little or no effect on serious adverse events or hospitalisation for hypercalcaemia, and the evidence is very uncertain about the effect of parathyroidectomy on other short-term outcomes, such as BMD, all-cause mortality and quality of life. The high uncertainty of evidence limits the applicability of our findings to clinical practice; indeed, this systematic review provides no new insights with regard to treatment decisions for people with (asymptomatic) PHPT. In addition, the methodological limitations of the included studies, and the characteristics of the study populations (mainly comprising white women with asymptomatic PHPT), warrant caution when extrapolating the results to other populations with PHPT. Large-scale multi-national, multi-ethnic and long-term RCTs are needed to explore the potential short- and long-term benefits of parathyroidectomy compared to non-surgical treatment options with regard to osteoporosis or osteopenia, urolithiasis, hospitalisation for acute kidney injury, cardiovascular disease and quality of life.
Topics: Male; Female; Humans; Aged; Hypercalcemia; Hyperparathyroidism, Primary; Parathyroidectomy; Cardiovascular Diseases; Parathyroid Hormone; Osteoporosis; Randomized Controlled Trials as Topic
PubMed: 36883976
DOI: 10.1002/14651858.CD013035.pub2