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The role of Rapid Intraoperative Parathyroid Hormone (ioPTH) assay in determining outcome of parathyroidectomy in primary hyperparathyroidism: A systematic review and meta-analysis.
Medas, F, Cappellacci, F, Canu, GL, Noordzij, JP, Erdas, E, Calò, PG
International journal of surgery (London, England). 2021;:106042
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Abstract
BACKGROUND Primary hyperparathyroidism (PHPT) is a common endocrine disorder. In the last few decades, the introduction of Rapid Intraoperative Parathyroid Hormone (ioPTH) monitoring has allowed to ensurance of the excision of all hyperfunctioning parathyroid tissues, reducing the risks of persistent and recurrent PHPT. However, the use of ioPTH is still debated among endocrine surgeons. MATERIAL AND METHODS The objective of this systematic review and meta-analysis was to assess if ioPTH monitoring is able to reduce the incidence of persistent or recurrent PHPT. A systematic literature search was performed using PubMed, Scopus, ISI-Web of Science and Cochrane Library Database. Prospective and retrospective studies addressing the efficacy of ioPTH monitoring were included in the systematic review and meta-analysis. The random-effects model was assumed to account for different sources of variation among studies. The overall effect size was computed through the inverse variance method. Heterogeneity across studies, possible outlier studies, and publication bias were evaluated. RESULTS A total of 28 studies with 13,323 patients were included in the quantitative analysis. The incidence of operative failure was 3.2% in the case group and 5.8% in the control group. After excluding three outlier studies, the quantitative analysis revealed that ioPTH reduced significantly the incidence of postoperative persistent or recurrent PHPT. (Risk Difference = -0.02; CI = -0.03, -0.01; p < 0.001). There was no evidence of heterogeneity among the studies (Q = 19.92, p = 0.70; I2 = 0%). The analysis of several continuous moderators revealed that the effectiveness of ioPTH was larger in studies with lower preoperative serum calcium values and higher incidences of multiple gland disease. CONCLUSION ioPTH monitoring is effective in reducing the incidence of persistent and recurrent PHPT. Its routine use should be suggested in the next guidelines regarding management of PHPT.
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Vitamin D supplementation effects on the clinical outcomes of patients with coronary artery disease: a systematic review and meta-analysis.
Bahrami, LS, Ranjbar, G, Norouzy, A, Arabi, SM
Scientific reports. 2020;(1):12923
Abstract
In this systematic review and meta-analysis our aim was to assess the effect of vitamin D supplementation on cardiac outcomes in patients with coronary artery disease (CAD). The search terms were performed from January 2000 to January 2018, only randomized clinical trials (RCT) in human subjects were considered, with no language restrictions. The electronic databases used in this study were: PubMed; Cochran library; Embase; and Scopus. Two independent expert reviewers carried out data extraction according to Cochrane recommendations. Only four RCTs were found in relation to the effects of vitamin D supplementation on the coronary artery disease. In these 299 patients, vitamin D supplementation had significant favorable effects on Diastolic Blood Pressure (DBP) (- 2.96, p = 0.02) and Parathyroid hormone (PTH) (- 4.05, p < 0.001). However, it had no significant effects on hs-CRP mean difference (- 0.04, p = 0.25), total cholesterol (TC) (- 0.46, p = 0.83), triglyceride (TG) (0.68, p = 0.89), low-density lipoproteins (LDL) (2.08, p = 0.56), and high-density lipoproteins (HDL) (- 2.59, p = 0.16). In conclusion, the use of vitamin D was associated with improvements in some cardiac outcomes of CAD patients with vitamin D deficiency. Also, further research is needed to clarify these results.
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Minimally invasive parathyroidectomy guided by intraoperative parathyroid hormone monitoring (IOPTH) and preoperative imaging versus bilateral neck exploration for primary hyperparathyroidism in adults.
Ahmadieh, H, Kreidieh, O, Akl, EA, El-Hajj Fuleihan, G
The Cochrane database of systematic reviews. 2020;(10):CD010787
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Abstract
BACKGROUND Bilateral neck exploration (BNE) is the traditional approach to sporadic primary hyperparathyroidism. With the availability of the preoperative imaging techniques and intraoperative parathyroid hormone assays, minimally invasive parathyroidectomy (MIP) is fast becoming the favoured surgical approach. OBJECTIVES To assess the effects of minimally invasive parathyroidectomy (MIP) guided by preoperative imaging and intraoperative parathyroid hormone monitoring versus bilateral neck exploration (BNE) for the surgical management of primary hyperparathyroidism. SEARCH METHODS We searched CENTRAL, MEDLINE, WHO ICTRP and ClinicalTrials.gov. The date of the last search of all databases was 21 October 2019. There were no language restrictions applied. SELECTION CRITERIA We included randomised controlled trials comparing MIP to BNE for the treatment of sporadic primary hyperparathyroidism in persons undergoing surgery for the first time. DATA COLLECTION AND ANALYSIS Two review authors independently screened titles and abstracts for relevance. Two review authors independently screened for inclusion, extracted data and carried out risk of bias assessment. The content expert senior author resolved conflicts. We assessed studies for overall certainty of the evidence using the GRADE instrument. We conducted meta-analyses using a random-effects model and performed statistical analyses according to the guidelines in the latest version of the Cochrane Handbook for Systematic Reviews of Interventions. MAIN RESULTS We identified five eligible studies, all conducted in European university hospitals. They included 266 adults, 136 participants were randomised to MIP and 130 participants to BNE. Data were available for all participants post-surgery up to one year, with the exception of missing data for two participants in the MIP group and for one participant in the BNE group at one year. Nine participants in the MIP group and 11 participants in the BNE group had missing data at five years. No study had a low risk of bias in all risk of bias domains. The risk ratio (RR) for success rate (eucalcaemia) at six months in the MIP group compared to the BNE group was 0.98 (95% confidence interval (CI) 0.94 to 1.03; P = 0.43; 5 studies, 266 participants; very low-certainty evidence). A total of 132/136 (97.1%) participants in the MIP group compared with 129/130 (99.2%) participants in the BNE group were judged as operative success. At five years, the RR was 0.94 (95% CI 0.83 to 1.08; P = 0.38; 1 study, 77 participants; very low-certainty evidence). A total of 34/38 (89.5%) participants in the MIP group compared with 37/39 (94.9%) participants in the BNE group were judged as operative success. The RR for the total incidence of perioperative adverse events was 0.50, in favour of MIP (95% CI 0.33 to 0.76; P = 0.001; 5 studies, 236 participants; low-certainty evidence). Perioperative adverse events occurred in 23/136 (16.9%) participants in the MIP group compared with 44/130 (33.9%) participants in the BNE group. The 95% prediction interval ranged between 0.25 and 0.99. These adverse events included symptomatic hypocalcaemia, vocal cord palsy, bleeding, fever and infection. Fifteen of 104 (14.4%) participants experienced symptomatic hypocalcaemia in the MIP group compared with 26/98 (26.5%) participants in the BNE group. The RR for this event comparing MIP with BNE at two days was 0.54 (95% CI 0.32 to 0.92; P = 0.02; 4 studies, 202 participants). Statistical significance was lost in sensitivity analyses, with a 95% prediction interval ranging between 0.17 and 1.74. Five out of 133 (3.8%) participants in the MIP group experienced vocal cord paralysis compared with 2/128 (1.6%) participants in the BNE group. The RR for this event was 1.87 (95% CI 0.47 to 7.51; P = 0.38; 5 studies, 261 participants). The 95% prediction interval ranged between 0.20 and 17.87. The effect on all-cause mortality was not explicitly reported and could not be adequately assessed (very low-certainty evidence). There was no clear difference for health-related quality of life between the treatment groups in two studies, but studies did not report numerical data (very low-certainty evidence). There was a possible treatment benefit for MIP compared to BNE in terms of cosmetic satisfaction (very low-certainty evidence). The mean difference (MD) for duration of surgery comparing BNE with MIP was in favour of the MIP group (-18 minutes, 95% CI -31 to -6; P = 0.004; 3 studies, 171 participants; very low-certainty evidence). The 95% prediction interval ranged between -162 minutes and 126 minutes. The studies did not report length of hospital stay. Four studies reported intraoperative conversion rate from MIP to open procedure information. Out of 115 included participants, there were 24 incidences of conversion, amounting to a conversion rate of 20.8%. AUTHORS' CONCLUSIONS The success rates of MIP and BNE at six months were comparable. There were similar results at five years, but these were only based on one study. The incidence of perioperative symptomatic hypocalcaemia was lower in the MIP compared to the BNE group, whereas the incidence of vocal cord paralysis tended to be higher. Our systematic review did not provide clear evidence for the superiority of MIP over BNE. However, it was limited by low-certainty to very low-certainty evidence.
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A comparison of the effect of supplementation and sunlight exposure on serum vitamin D and parathyroid hormone: A systematic review and meta-analysis.
Moradi, S, Shahdadian, F, Mohammadi, H, Rouhani, MH
Critical reviews in food science and nutrition. 2020;(11):1881-1889
Abstract
Background: Supplementation and getting sunlight exposure are two treatments for vitamin D deficiency. However, studies reported conteroversial findings regarding the efficacy of these two methods.Objective: To compare the effect of oral vitamin D supplementation with sunlight exposure on serum vitamin D and parathyroid hormone (PTH).Methods: A computer-based literature search through PubMed, Scopus and Google scholar search engines was conducted until April 2019 to find clinical trials which compared the effect of oral vitamin D supplementation with sunlight exposure on serum vitamin D and PTH. Means for serum 25-hydroxy vitamin D3 (25(OH) D3) and PTH concentration were extracted. A subgroup analysis was used to detect potential sources of inter-study heterogeneity. Mean differences (MD) were analyzed using a random-effects model (the DerSimonian-Laird approach).Results: A total of seven papers were included in the meta-analysis. Pooled analysis showed that vitamin D supplementation significantly elevated levels of serum 25(OH) D3 in comparison with sunlight exposure (MD: 8.56nmol/l, 95%CI: 4.15, 12.97, T2 = 40.32%, H2 = 9.45%, P for heterogeneity p < 0.001). Also, the difference between the effect of vitamin D supplementation and sun exposure was lower in studies which used UVB radiation compared with studies which applied direct sunlight (MD: 11.65 nmol/l, 95%CI: 7.02, 16.28; P for between subgroup heterogeneity = 0.001).Conclusion: Vitamin D supplementation was more effective than sun exposure at increasing serum 25(OH) D3. The difference between efficacy of vitamin D supplementation and sun exposure was lower in studies which used long-term sun exposure or applied UVB treatment instead of direct sunlight.
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The effectiveness and safety of parathyroid hormone in fracture healing: A meta-analysis.
Hong, H, Song, T, Liu, Y, Li, J, Jiang, Q, Song, Q, Deng, Z
Clinics (Sao Paulo, Brazil). 2019;:e800
Abstract
The very large economic and social burdens of fracture-related complications make rapid fracture healing a major public health goal. The role of parathyroid hormone (PTH) in treating osteoporosis is generally accepted, but the effect of PTH on fracture healing is controversial. This meta-analysis was designed to investigate the efficacy and safety of PTH in fracture healing. The EMBASE, PubMed, and Cochrane Library databases were systematically searched from the inception dates to April 26, 2018. The primary randomized clinical trials comparing PTH treatment for fracture healing with placebo or no treatment were identified. We did not gain additional information by contacting the authors of the primary studies. Two reviewers independently extracted the data and evaluated study quality. This meta-analysis was executed to determine the odds ratio, mean difference, standardized mean difference, and 95% confidence intervals with random-effects models. In total, 8 randomized trials including 524 patients met the inclusion criteria. There were significant differences in fracture healing time, pain relief and function improvement. There were no significant differences in the fracture healing rate or adverse events, including light-headedness, hypercalcemia, nausea, sweating and headache, except for slight bruising at the injection site. We determined that the effectiveness and safety of PTH in fracture healing is reasonably well established and credible.
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Long-term effects on PTH and mineral metabolism of 1.25 versus 1.75 mmol/L dialysate calcium in peritoneal dialysis patients: a meta-analysis.
Jin, L, Zhou, J, Shao, F, Yang, F
BMC nephrology. 2019;(1):213
Abstract
BACKGROUND This study aimed to compare 1.25 and 1.75 mmol/L dialysate calcium for their effects on parathyroid hormone (PTH) and mineral metabolism in peritoneal dialysis (PD). METHODS The PubMed, Cochrane Library, and EmBase databases were searched from inception to October 2016. Methodological quality assessment of the included studies was performed using the risk of bias tool of the Review Manager software. The meta-analysis was carried out with the Stata12.0 software. Subgroup analysis was performed by study design [randomized controlled trial (RCT) and non-RCT]. Odds ratios or standardized mean differences were used to assess the outcome measures, including intact parathyroid hormone (i-PTH) levels, serum total calcium amounts, ionized calcium levels, phosphate concentrations, and peritonitis episodes. RESULTS Seven studies were enrolled in the synthesized analysis, including 4 RCTs and 3 non-RCTs. All studies compared 1.25 mmol/L and 1.75 mmol/L dialysate calcium for PD. Pooled analysis revealed that 1.75 mmol/L dialysate calcium significantly reduced i-PTH levels compared with the 1.25 mmol/L dose in PD patients. However, 1.25 mmol/L dialysate calcium was superior to the 1.75 mmol/L dose in decreasing the levels of serum total calcium and ionized calcium in PD patients. No significant differences in phosphate amounts and peritonitis episodes were observed between the two groups. CONCLUSION These findings indicated that 1.75 mmol/L dialysate calcium is more appropriate for PD patients with secondary hyperparathyroidism. Meanwhile, 1.25 mmol/L dialysate calcium is more favorable to PD patients with secondary hypercalcemia. However, further well-designed and high-quality studies are required to validate these findings.
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Genome-wide meta-analysis identifies novel loci associated with parathyroid hormone level.
Matana, A, Brdar, D, Torlak, V, Boutin, T, Popović, M, Gunjača, I, Kolčić, I, Boraska Perica, V, Punda, A, Polašek, O, et al
Molecular medicine (Cambridge, Mass.). 2018;(1):15
Abstract
BACKGROUND Parathyroid hormone (PTH) is one of the principal regulators of calcium homeostasis. Although serum PTH level is mostly accounted by genetic factors, genetic background underlying PTH level is insufficiently known. Therefore, the aim of this study was to identify novel genetic variants associated with PTH levels. METHODS We performed GWAS meta-analysis within two genetically isolated Croatian populations followed by replication analysis in a Croatian mainland population and we also combined results across all three analyzed populations. The analyses included 2596 individuals. A total of 7,411,206 variants, imputed using the 1000 Genomes reference panel, were analysed for the association. In addition, a sex-specific GWAS meta-analyses were performed. RESULTS Polymorphisms with the lowest P-values were located on chromosome 4 approximately 84 kb of the 5' of RASGEF1B gene. The most significant SNP was rs11099476 (P = 1.15 × 10-8). Sex-specific analysis identified genome-wide significant association of the variant rs77178854, located within DPP10 gene in females only (P = 2.21 × 10- 9). There were no genome-wide significant findings in the meta-analysis of males. CONCLUSIONS We identified two biologically plausible novel loci associated with PTH levels, providing us with further insights into the genetics of this complex trait.
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Effects of different phosphate lowering strategies in patients with CKD on laboratory outcomes: A systematic review and NMA.
Sekercioglu, N, Angeliki Veroniki, A, Thabane, L, Busse, JW, Akhtar-Danesh, N, Iorio, A, Cruz Lopes, L, Guyatt, GH
PloS one. 2017;(3):e0171028
Abstract
BACKGROUND Chronic kidney disease-mineral and bone disorder (CKD-MBD), a complication of chronic kidney disease, has been linked to reduced quality and length of life. High serum phosphate levels that result from CKD-MBD require phosphate-lowering agents, also known as phosphate binders. The objective of this systematic review is to compare the effects of available phosphate binders on laboratory outcomes in patients with CKD-MBD. METHODS Data sources included MEDLINE and EMBASE from January 1996 to April 2016, and the Cochrane Register of Controlled Trials up to April 2016. Teams of two reviewers, independently and in duplicate, screened titles and abstracts and potentially eligible full text reports to determine eligibility, and subsequently abstracted data and assessed risk of bias in eligible randomized controlled trials (RCTs). Eligible trials enrolled patients with CKD-MBD and randomized them to receive calcium-based phosphate binders (delivered as calcium acetate, calcium citrate or calcium carbonate), non-calcium-based phosphate binders (NCBPB) (sevelamer hydrochloride, sevelamer carbonate, lanthanum carbonate, sucroferric oxyhydroxide and ferric citrate), phosphorus restricted diet (diet), placebo or no treatment and reported effects on serum levels of phosphate, calcium and parathyroid hormone. We performed Bayesian network meta-analyses (NMA) to calculate the effect estimates (mean differences) and 95% credible intervals for serum levels of phosphate, calcium and parathyroid hormone. We calculated direct, indirect and network meta-analysis estimates using random-effects models. We applied the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to rate the quality of evidence for each pairwise comparison. RESULTS Our search yielded 1108 citations; 71 RCTs were retrieved for full review and 16 proved eligible. Including an additional 13 studies from a previous review, 29 studies that enrolled 8335 participants proved eligible; 26 trials provided data for quantitative synthesis. Sevelamer, lanthanum, calcium, iron, diet and combinations of active treatments (calcium or sevelamer or lanthanum and combination of calcium and sevelamer) resulted in significantly lower serum phosphate as compared to placebo (moderate to very low quality of evidence). We found no statistically significant differences between active treatment categories in lowering serum phosphate. Sevelamer, lanthanum and diet resulted in lower serum calcium compared to calcium (moderate quality evidence for lanthanum and diet; low quality evidence for Sevelamer). Iron, sevelamer and calcium yielded lower parathyroid hormone levels as compared to lanthanum. Meta-regression analyses did not yield a statistically significant association between treatment effect and trial duration. DISCUSSION/CONCLUSIONS We found few differences between treatments in impact on phosphate and differences in parathyroid hormone. Relative to calcium, sevelamer, lanthanum and diet showed significant reduction in serum calcium from baseline. Treatment recommendations should be based on impact on patient-important outcomes rather than on surrogate outcomes. Systematic review registration: PROSPERO CRD-42016032945.
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Serum Parathyroid Hormone Responses to Vitamin D Supplementation in Overweight/Obese Adults: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.
Lotito, A, Teramoto, M, Cheung, M, Becker, K, Sukumar, D
Nutrients. 2017;(3)
Abstract
Obesity is often associated with vitamin D deficiency and secondary hyperparathyroidism. Vitamin D supplementation typically leads to the reductions in serum parathyroid hormone (PTH) levels, as shown in normal weight individuals. Meanwhile, the dose of vitamin D supplementation for the suppression of PTH may differ in overweight and obese adults. We conducted a systematic review and meta-analysis of randomized controlled trials to determine the dose of vitamin D supplementation required to suppress PTH levels in overweight/obese individuals. We identified 18 studies that examined overweight or obese healthy adults who were supplemented with varying doses of vitamin D3. The primary outcomes examined were changes in PTH and serum 25-hydroxyvitamin D (25OHD) levels from baseline to post-treatment. The results of the meta-analysis showed that there was a significant treatment effect of vitamin D supplementation on PTH, total standardized mean difference (SMD) (random effects) = -0.38 (95% CI = -0.56 to -0.20), t = -4.08, p < 0.001. A significant treatment effect of vitamin D supplementation was also found on 25OHD, total SMD (random effects) = 2.27 (95% CI = 1.48 to 3.06) t = 5.62, p < 0.001. Data from available clinical trials that supplemented adults with D3 ranging from 400 IU to 5714 IU, showed that 1000 IU of vitamin D supplementation best suppressed serum PTH levels, total SMD = -0.58, while vitamin D supplementation with 4000 IU showed the greatest increase in serum 25OH levels. Vitamin D and calcium supplementation of 700 IU and 500 mg, respectively, also showed a significant treatment effect on the suppression of PTH with a total SMD = -5.30 (95% CI = -9.72 to -0.88). In conclusion, the meta analysis of available clinical trials indicates that 1000 IU vitamin D supplementation can suppress serum PTH levels, while 4000 IU of vitamin D was associated with the largest increase in serum 25OHD levels in the overweight and obese population.
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Cinacalcet versus standard treatment for chronic kidney disease: a systematic review and meta-analysis.
Sekercioglu, N, Busse, JW, Sekercioglu, MF, Agarwal, A, Shaikh, S, Lopes, LC, Mustafa, RA, Guyatt, GH, Thabane, L
Renal failure. 2016;(6):857-74
Abstract
BACKGROUND Chronic kidney disease-mineral and bone disorders (CKD-MBD) have been associated with poor health outcomes, including diminished quality and length of life. Standard management for CKD-MBD includes phosphate restricted diet, vitamin D and phosphate binders. Persistently elevated parathyroid hormone levels may require the addition of cinacalcet hydrochloride (cinacalcet), which sensitizes calcium receptors in the parathyroid gland. PURPOSE The objective of this systematic review is to compare, in patients with CKD-MBD the effect of cinacalcet versus standard treatment on patient-important outcomes, including parathyroidectomy, fractures, hospitalizations due to cardiovascular events, cardiovascular mortality, all-cause mortality, and intermediate outcomes, in particular Kidney Disease Outcome Quality Initiative targets. METHODS Data sources included MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and Web of Science from 1996 to June 2015. Teams of two reviewers, independently and in duplicate, screened titles and abstracts and potentially eligible full text reports to determine eligibility, and subsequently abstracted data and assessed risk of bias in eligible trials. We calculated the effect estimates (risk ratios or mean differences) and 95% confidence intervals, as well as statistical measures of variability in results across studies using random effect models. We used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to rate quality of evidence about estimates of effect on an outcome-by-outcome basis for all outcomes. We presented our results with a GRADE summary table. RESULTS Twenty-four trials including 8311 CKD patients proved eligible. The results left considerable uncertainty regarding the impact of cinacalcet on reducing fractures (relative risk [RR] 0.59, 95% confidence interval [CI] 0.13-2.60; heterogeneity: p = 0.03, I(2)= 78%; very low quality evidence), and indicated that cinacalcet did not reduce hospitalizations due to cardiovascular events (RR 0.93, 95% CI 0.85-1.02, moderate quality of evidence), cardiovascular mortality (RR 0.95, 95% CI 0.84-1.07; heterogeneity p= 0.61, high quality evidence) or all-cause mortality (RR 0.96, 95% CI 0.89-1.04; heterogeneity: p= 0.98, I(2)= 0%; moderate quality evidence). Cinacalcet reduced the need for parathyroidectomy (RR 0.30, 95% CI 0.22-0.42; heterogeneity: p= 0.70, I(2)= 0%; absolute effect 55 fewer per 1000 [95% CI 61 fewer to 45 fewer], high quality of evidence). The most common adverse event associated with cinacalcet therapy was gastrointestinal side effects. Cinacalcet increased nausea (RR 2.16, 95% CI 1.46-3.21, absolute effect 158 more per 1000 [95% CI 82 more to 302 more]) and vomiting (RR 2.15, 95% CI 1.66-2.80, absolute effect 63 more per 1000 [95% CI 109 more to 171 more]). Cinacalcet treatment increased the rate of hypocalcemia (RR 6.0, 95% CI 3.65-9.87; heterogeneity: p= 0.71, I(2)= 0%, absolute effect 20 more per 1000 [95% CI 11 more to 36 more], high quality of evidence). CONCLUSIONS In the hands of clinicians participating in these studies, cinacalcet decreased the rate of parathyroidectomy but had no influence on mortality. Patients and clinicians can trade of the benefit of fewer parathyroidectomies against the adverse effects.