Primary Hyperparathyroidism Raises Fracture, CV Risk



Dr Mattias Lorentzon

Patients with untreated primary hyperparathyroidism show significant increases in the risk of hip fracture, cardiovascular events, and mortality, however, the risk is reduced when treated with parathyroidectomy, results from a large sample of patients in Sweden show.

“Our results indicate that the risk of these severe outcomes is lower after surgery than before, suggesting a clinical benefit from surgery,” senior author Mattias Lorentzon, MD, professor of physician geriatric medicine at the University of Gothenburg and chief at Sahlgrenska University Hospital, Sweden, told Medscape Medical News.

The results, recently published in JAMA Network Open, are from an analysis of data from hospitals in Sweden between July 2006 and December 2017, involving 16,374 patients diagnosed with primary hyperparathyroidism.

For the study, each patient was matched with 10 controls from the general population based on sex, birth year, and county of residence.

Overall, patients were a mean age of 67.5 years, and 78.2% were women, consistent with hyperparathyroidism being known to more commonly affect women.

With a mean follow-up of 1.2 years for patients with primary hyperparathyroidism and 4.6 years for controls, those with primary hyperparathyroidism had unadjusted increases in the risk of any fracture (hazard ratio [HR]1.39), hip fracture (HR, 1.51), having a cardiovascular event (HR, 1.45), and injurious falls, and a more than three times higher rate of kidney stones (HR, 3.65; all P < .001).

Their risk of all-cause and cardiovascular-related death was also higher versus controls (HR 1.72 and 1.73; both P < .001).

Hazard ratios for all outcomes declined after adjustment for key factors including age, sex, Charlson comorbidity index, and previous fracture, but remained significantly greater than controls (all P < .001, with the exception of hip fracture at P = .002).

Effects of Parathyroidectomy

Of the patients with primary hyperparathyroidism, 42.3% underwent a parathyroidectomy, the only definitive treatment for the condition, at a median of about 6 months after diagnosis. Those patients were younger bidities, had fewer comorbidities, and had lower risks of fracture and cardiovascular events.

Compared with those who did not receive the surgery, patients treated with parathyroidectomy had significant reductions in all outcomes after adjustment, including hip fracture (HR, 0.78; P = .04), any fracture (HR, 0.83; P = .001), injurious fall (HR, 0.83; P < .001), all-cause death (HR, 0.59; P < .001), and cardiovascular-related death (HR, 0.60; P < .001).

“The study indicates that surgery clearly reduces the risk of osteoporosis fractures, fall injuries, and death in cardiovascular events, and these are vital findings that may lead to more patients being selected for surgery,” said Lorentzon in a press statement.

Previous studies have specifically shown impaired bone properties in trabecular as well as cortical bone in patients with primary hyperparathyroidism, and a meta-analysis of numerous smaller studies also showed an increased risk of any fracture, vertebral fracture, and forearm fracture with hyperparathyroidism.

“Results of the present study, which used a substantially larger dataset, are in agreement with these previous analyses,” the authors write.

Despite the reports, there has been some debate over the benefits of parathyroidectomy, with a recent randomized controlled trial showing no benefit of the surgery on fracture, CV risk, or mortality, as reported by Medscape Medical News.

However, that study focused on patients with mild hyperparathyroidism.

Lorentzon commented to Medscape Medical News that the randomized trial also “lacked the statistical power to investigate more rare outcomes such as fracture risk or risk of cardiovascular events.”

“In our study, all cases diagnosed were included, [with results showing that] more serious disease is likely to benefit more from surgical treatment than mild,” he said.

Among caveats with the current study is that the patients were all untreated, meaning the results may not necessarily extend to those who have received other treatments for hyperparathyroidism, Lorentzon added.

Commenting to Medscape Medical NewsMikkel Pretorius, MD, who was first author of the randomized trial of patients with mild hyperparathyroidism, and his co-authors, said they “congratulate the authors on the publication [and] Agree that there is a need to better understand the risks involved [with hyperparathyroidism].”

“Further investigation and focus on this common endocrine disorder is needed,” said Pretorius, of the Section of Specialized Endocrinology, Oslo University Hospital, Rikshospitalet, Norway, and colleagues.

Which Understanding Patients Are Most at Risk

Pretorius and colleagues noted that a challenge with the inclusion of a broader range of patients in the current study is understanding which patients are most at risk.

“The fact that the study does not identify or exclude the patients with severe disease or organ manifestations who [meet criteria for parathyroidectomy] making interpretation difficult,” they said.

They point to the reductions in HRs after multivariate adjustment, which underscore “that the [higher risks] could be due to other factors,” they said.

For instance, even if all patients were untreated for hyperparathyroidism, those who were hospitalized could nevertheless likely have had more treatment with a wide array of other medications, such as prednisolone or opioids.

“The potential biases comparing two such groups are many and hard to quantify through retrospective registry data,” they said.

The study was funded by the Swedish Research Council and Sahlgrenska University Hospital. Lorentzon has reported receiving personal fees from Amgen, Astellas, Lilly, Meda, Renapharma, Radius Health, UCB Pharma, and Consilient Health outside the submitted work. Pretorius has reported no relevant financial relationships.

JAMA Netw Open. Published June 3, 2022. Full text

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