Primary hyperparathyroidism associated with an increased risk of fractures and cardiovascular events

1. In this cohort study, among 16 374 Swedish adult patients with primary hyperparathyroidism, the risk hip fracture was increased by 51%, and risk of cardiovascular events increased by 45% compared to matched healthy participants.

2. Parathyroidectomy was associated with a reduced risk of any fracture, hip fracture, cardiovascular events and death.

Evidence Rating Level: 2 (Good)

Study Rundown: Primary hyperparathyroidism (pHPT) is an endocrine disorder in which individuals have an elevated serum calcium combined with a normal or high blood level of parathyroid hormone. Known concerns of pHPT include increased bone loss and an elevated risk of fractures at sites including the spine, wrist, ribs and pelvis. As such, this retrospective cohort study investigated whether untreated pHPT was associated with an increased risk of fractures and cardiovascular events (CVEs) in comparison with the risk of a sex, age and country-matched control group and whether parathyroidectomy was associated with a reduction in these outcomes. The study included patients who were diagnosed with pHPT at hospitals in Sweden between 2006 to 2017. The primary outcomes were fractures, CVEs, and death. A total of 16 374 patients with pHPT were identified with a mean age of 67.5 years. Compared with the control group, the pHPT group was found to have a higher risk of any fracture by 39%, hip fracture by 51%, CVEs 45% and death 72%. Parathyroidectomy was associated with a reduced risk of any fracture by 17% and death by 59%. A major strength of this study was that in terms of the number of patients with untreated pHPT and multiple observed outcomes, it is the largest analysis performed thus far. As a result of the observational design however, a limitation to this study is that it could not establish causality, although the time-dependent analysis suggested an association between parathyroidectomy and reduced risk of fractures, CVEs and death.

Click to read the study in JAMA Network Open

Relevant Reading: Survival after the diagnosis of primary hyperparathyroidism: a population-based study

In-Depth [retrospective cohort]: This study investigated whether primary hyperparathyroidism (pHPT) was associated with an increased risk of fractures, CVEs and mortality, compared to the risk of a sex, age and country-matched control group. Data was collected from patients diagnosed with pHPT at hospitals in Sweden between July 1, 2006 to December 31, 2017. Each patient was matched with 10 control individuals from the general population. A total of 16 374 patients with pHPT were identified (mean SD age, 67.5 [12.9] years; 12806 women [78.2%]), with 163 740 control individuals. The median follow-up time for the pHPT group was 1.15 (.040-4.06) years and for the control it was 4.62 (2.08-7.51) years. Patients with pHPT had significantly higher risks of any fracture (unadjusted HR, 1.39; 95% CI, 1.31-1.48), major osteoporotic fracture (unadjusted HR, 1.43; 95% CI, 1.33-1.54), hip fracture (unadjusted HR, 1.51; 95% CI, 1.35-1.70), and injurious fall (unadjusted HR, 1.51; 95% CI, 1.42-1.60) compared with those in the control group. The risk of fractures was significantly increased at the following sites: wrist (unadjusted HR, 1.34; 95 CI, 1.18-1.52), upper arm (unadjusted HR, 1.46; 95% CI, 1.25-1.71) and lower leg (unadjusted HR, 1.31; 95% CI, 1.12-1.54). The risk of any CVE for patients with pHPT was increased (unadjusted HR, 1.45; 95% CI, 1.34-1.57), as well as the risk for acute myocardial infarction (unadjusted HR, 1.39; 95% CI, 1.24-1.56) and ischemic stroke (unadjusted HR, 1.51; 95%CI, 1.36-1.68). The risk of death (unadjusted HR, 1.72; 95% CI, 1.65-1.80) was also increased in higher in patients with pHPT compared to the control group. There was a substantial increase in the risk of kidney stones, almost 4 times higher in patients with pHPT (unadjusted HR, 3.65; 95% CI, 3.27-4.08) than in control individuals. Of the 16 374 patients with pHPT, 6934 (42.3%) underwent a parathyroidectomy. While using the Poisson regression model to study the pHPT group separately, parathyroidectomy was found to be associated with a reduced risk of hip fracture (HR, 0.78; 95% CI, 0.61-0.98), any fracture (HR, 0.83; 95% CI, 0.75-0.93), injurious fall (HR, 0.83; 95% CI, 0.74-0.92), CVE (HR, 0.84; 95% CI, 0.73-0.97), and death (HR, 0.59; 95% CI, 0.53-0.65).

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