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Analysis of comorbidities, clinical outcomes, and parathyroidectomy in adults with primary hyperparathyroidism

Analysis of comorbidities, clinical outcomes, and parathyroidectomy in adults with primary hyperparathyroidism
Analysis of comorbidities, clinical outcomes, and parathyroidectomy in adults with primary hyperparathyroidism
Importance: patients with primary hyperparathyroidism (pHPT) appear to have an increased risk of fractures and other comorbidities, such as cardiovascular disease, although results from previous studies have been inconsistent. Evidence of the association of parathyroidectomy (PTX) with these outcomes is also limited because of the lack of large well-controlled trials.

Objective: to investigate whether untreated pHPT was associated with an increased risk of incident fractures and cardiovascular events (CVEs) and whether PTX was associated with a reduced risk of these outcomes.

Design, Setting, and Participants: this cohort study included all patients who were diagnosed with pHPT at hospitals in Sweden between July 1, 2006, and December 31, 2017. Each patient was matched with 10 control individuals from the general population by sex, birth year, and county of residence. The patients were followed up until December 31, 2017. Data analyses were performed from October 2021 to April 2022.

Main Outcomes and Measures: the primary outcomes were fractures, CVEs, and death. Cumulative incidence of events was estimated using the 1-minus Kaplan-Meier estimator of corresponding survival function. Cox proportional hazards regression models were used to calculate hazard ratios (HRs).

Results: a total of 16 374 patients with pHPT were identified (mean [SD] age, 67.5 [12.9] years; 12 806 women [78.2%]), with 163 740 control individuals. The follow-up time was 42 310 person-years for the pHPT group and 803 522 person-years for the control group. Compared with the control group, the pHPT group had a higher risk of any fracture (unadjusted HR, 1.39; 95% CI, 1.31-1.48), hip fracture (unadjusted HR, 1.51; 95% CI, 1.35-1.70), CVEs (unadjusted HR, 1.45; 95% CI, 1.34-1.57), and death (unadjusted HR, 1.72; 95% CI, 1.65-1.80). In a time-dependent Poisson regression model, PTX was associated with a reduced risk of any fracture (HR, 0.83; 95% CI, 0.75-0.93), hip fracture (HR, 0.78; 95% CI, 0.61-0.98), CVEs (HR, 0.84; 95% CI, 0.73-0.97), and death (HR, 0.59; 95% CI, 0.53-0.65).

Conclusions and Relevance Results of this study suggest that pHPT is associated with increased risk of fractures, CVEs, and death, highlighting the importance of identifying patients with this condition to prevent serious unfavorable outcomes. The reduced risk of these outcomes associated with PTX suggests a clinical benefit of surgery.
Adult, Aged, Cohort Studies, Female, Hip Fractures/epidemiology, Humans, Hyperparathyroidism, Primary/complications, Parathyroidectomy/methods, Proportional Hazards Models
Axelsson, Kristian F.
1b319953-04ae-4f73-b221-dd56fd312993
Wallander, Marit
bb43c064-c4e1-4ca9-8582-645c15fc0cf9
Johansson, Helena
04f12338-4dd1-437b-b9bc-e0884130c215
Harvey, Nicholas
ce487fb4-d360-4aac-9d17-9466d6cba145
Vandenput, Liesbeth
0910d143-4b58-4579-82b0-3810272f1814
McCloskey, Eugene
6d3df4aa-b438-4a83-bd06-06b6cbe3980f
Liu, Enwu
08027c15-9e71-44bb-9623-3081f5f6492d
Kanis, John A.
f1621d8d-8afb-4d97-9679-2165d88a344d
Litsne, Henrik
e95cdd34-5e70-482e-a53c-45189411cd14
Lorentzen, Mattias
72997ee0-d7ba-42b1-912e-f60414366449
Axelsson, Kristian F.
1b319953-04ae-4f73-b221-dd56fd312993
Wallander, Marit
bb43c064-c4e1-4ca9-8582-645c15fc0cf9
Johansson, Helena
04f12338-4dd1-437b-b9bc-e0884130c215
Harvey, Nicholas
ce487fb4-d360-4aac-9d17-9466d6cba145
Vandenput, Liesbeth
0910d143-4b58-4579-82b0-3810272f1814
McCloskey, Eugene
6d3df4aa-b438-4a83-bd06-06b6cbe3980f
Liu, Enwu
08027c15-9e71-44bb-9623-3081f5f6492d
Kanis, John A.
f1621d8d-8afb-4d97-9679-2165d88a344d
Litsne, Henrik
e95cdd34-5e70-482e-a53c-45189411cd14
Lorentzen, Mattias
72997ee0-d7ba-42b1-912e-f60414366449

Axelsson, Kristian F., Wallander, Marit, Johansson, Helena, Harvey, Nicholas, Vandenput, Liesbeth, McCloskey, Eugene, Liu, Enwu, Kanis, John A., Litsne, Henrik and Lorentzen, Mattias (2022) Analysis of comorbidities, clinical outcomes, and parathyroidectomy in adults with primary hyperparathyroidism. JAMA Network Open, 5 (6), [e2215396]. (doi:10.1001/jamanetworkopen.2022.15396).

Record type: Article

Abstract

Importance: patients with primary hyperparathyroidism (pHPT) appear to have an increased risk of fractures and other comorbidities, such as cardiovascular disease, although results from previous studies have been inconsistent. Evidence of the association of parathyroidectomy (PTX) with these outcomes is also limited because of the lack of large well-controlled trials.

Objective: to investigate whether untreated pHPT was associated with an increased risk of incident fractures and cardiovascular events (CVEs) and whether PTX was associated with a reduced risk of these outcomes.

Design, Setting, and Participants: this cohort study included all patients who were diagnosed with pHPT at hospitals in Sweden between July 1, 2006, and December 31, 2017. Each patient was matched with 10 control individuals from the general population by sex, birth year, and county of residence. The patients were followed up until December 31, 2017. Data analyses were performed from October 2021 to April 2022.

Main Outcomes and Measures: the primary outcomes were fractures, CVEs, and death. Cumulative incidence of events was estimated using the 1-minus Kaplan-Meier estimator of corresponding survival function. Cox proportional hazards regression models were used to calculate hazard ratios (HRs).

Results: a total of 16 374 patients with pHPT were identified (mean [SD] age, 67.5 [12.9] years; 12 806 women [78.2%]), with 163 740 control individuals. The follow-up time was 42 310 person-years for the pHPT group and 803 522 person-years for the control group. Compared with the control group, the pHPT group had a higher risk of any fracture (unadjusted HR, 1.39; 95% CI, 1.31-1.48), hip fracture (unadjusted HR, 1.51; 95% CI, 1.35-1.70), CVEs (unadjusted HR, 1.45; 95% CI, 1.34-1.57), and death (unadjusted HR, 1.72; 95% CI, 1.65-1.80). In a time-dependent Poisson regression model, PTX was associated with a reduced risk of any fracture (HR, 0.83; 95% CI, 0.75-0.93), hip fracture (HR, 0.78; 95% CI, 0.61-0.98), CVEs (HR, 0.84; 95% CI, 0.73-0.97), and death (HR, 0.59; 95% CI, 0.53-0.65).

Conclusions and Relevance Results of this study suggest that pHPT is associated with increased risk of fractures, CVEs, and death, highlighting the importance of identifying patients with this condition to prevent serious unfavorable outcomes. The reduced risk of these outcomes associated with PTX suggests a clinical benefit of surgery.

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Accepted/In Press date: 17 April 2022
e-pub ahead of print date: 3 June 2022
Published date: 3 June 2022
Additional Information: Funding Information: Author Contributions: Drs Axelsson and Wallander had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: Axelsson, Johansson, Lorentzon. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: Axelsson, Kanis, Lorentzon. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Axelsson, Wallander, Johansson, Liu, Kanis, Litsne, Lorentzon. Obtained funding: Axelsson, Lorentzon. Administrative, technical, or material support: Wallander, Harvey, Lorentzon. Supervision: Wallander, Johansson, Lorentzon. Conflict of Interest Disclosures: Dr Axelsson reported receiving personal fees from Lilly, Meda/Mylan, and Amgen. Dr Wallander reported receiving personal fees from Amgen. Dr Harvey reported receiving personal fees from Alliance for Better Bone Health, Amgen, MSD, Eli Lilly, Servier, Shire, UCB Pharma, Kyowa Kirin, Consilient Health, Radius Health, and Internis Pharma. Dr McCloskey reported receiving research funding and personal fees from Amgen, AstraZeneca, Consilient Health, Fresenius Kabi, GlaxoSmithKline, Hologic, Internis, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi-Aventis, Servier, Synexus, UCB Pharma, Unilever, and Warner Chilcott. Dr Kanis reported receiving grants from Amgen, Lilly, and Radius Health. Dr Lorentzon reported receiving personal fees from Amgen, Astellas, Lilly, Meda, Renapharma, Radius Health, UCB Pharma, and Consilient Health outside the submitted work. No other disclosures were reported. Funding Information: Funding/Support: This study was funded by the Swedish Research Council, Sahlgrenska University Hospital, Västra Götalandsregionen. © 2022 Axelsson KF et al. JAMA Network Open.
Keywords: Adult, Aged, Cohort Studies, Female, Hip Fractures/epidemiology, Humans, Hyperparathyroidism, Primary/complications, Parathyroidectomy/methods, Proportional Hazards Models

Identifiers

Local EPrints ID: 467380
URI: http://eprints.soton.ac.uk/id/eprint/467380
PURE UUID: a755a285-09c5-4248-81dd-4b48bda12203
ORCID for Nicholas Harvey: ORCID iD orcid.org/0000-0002-8194-2512

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Date deposited: 07 Jul 2022 17:11
Last modified: 23 Jul 2022 01:52

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Contributors

Author: Kristian F. Axelsson
Author: Marit Wallander
Author: Helena Johansson
Author: Nicholas Harvey ORCID iD
Author: Liesbeth Vandenput
Author: Eugene McCloskey
Author: Enwu Liu
Author: John A. Kanis
Author: Henrik Litsne
Author: Mattias Lorentzen

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