Surgery Best to Reduce Fractures in Hyperparathyroidism

Pam Harrison

April 07, 2016

Management of primary hyperparathyroidism with a simple surgical procedure to remove the benign tumor from the parathyroid significantly reduces fracture risk over time, whereas treatment with any of the bisphosphonates increases the risk in the same patients, a new observational study indicates.

"These patients have a 5% chance of fracturing over 10 years — I would be afraid of that — it's more common than a car accident," lead author Michael Yeh, MD, chief of endocrine surgery at the David Geffen School of Medicine, Los Angeles, California, told Medscape Medical News.

"And while we believed for years that the bisphosphonates were an acceptable alternative for the treatment of osteoporosis caused by primary hyperparathyroidism, our evidence shows that parathyroid surgery is really the only thing that works to decrease fracture risk," he asserts.

The study was published online April 4 in the Annals of Internal Medicine.

Only 20% of Patients Underwent Surgery

Dr Yeh and colleagues explain that primary hyperparathyroidism is a common endocrine disorder, affecting one in 400 women and one in 1200 men in the United States. Untreated primary hyperparathyroidism leads to loss of bone-mineral density (BMD) over time, raising concern about the development of osteoporosis and associated elevated fracture risk.

They used the Kaiser Permanente Southern California Laboratory Management System to retrospectively identify patients who had a biochemical diagnosis of primary hyperparathyroidism between 1995 and 2010.

Patients had classically defined primary hyperparathyroidism, identified as a serum total calcium level >2.63 mmol/L  (>10.5 mg/dL) as well as an excess in parathyroid hormone (PTH) >65 ng/L.

BMD measurements were taken of the total hip and lumbar spine to the end of 2012.

Overall, the study involved 6272 patients with primary hyperparathyroidism, 36% of whom had osteopenia at baseline and 53% of whom had osteoporosis.

Some 22% of the group were treated with a bisphosphonate for a median duration of 55 months and another 22% underwent parathyroidectomy; the remaining 55% were kept under observation alone.

At a median follow-up of 4.5 years, investigators identified 940 fractures, 178 of them being fractures of the hip and 762 being fractures involving bones other than the hip.

Bisphosphonates Up Fracture Risk

"Across all time points, parathyroidectomy was associated with a reduced risk for any fracture, whereas bisphosphonates were associated with an increased risk," Dr Yeh and colleagues report.

Indeed, at 10 years, patients who had undergone parathyroid surgery had a 64% lower absolute risk for hip fracture and a 24% lower absolute risk for any fracture compared with patients who received no treatment, and this risk reduction was evident regardless of BMD at baseline.

The absolute risk for hip fracture at 10 years was 55.9 events per 1000 patients in those undergoing observation, 20.4 events per 1000 patients in those who had parathyroidectomy, and 85.6 events per 1000 patients in those treated with bisphosphonates.

The risk for any fracture at 10 years was 206.1 events per 1000 patients in those undergoing observation, 156.8 events per 1000 patients in those who had parathyroidectomy, and 302.5 events per 1000 patients in those treated with bisphosphonates.

Because patients with osteoporosis were more frequently prescribed a bisphosphonate, investigators went on to analyze the likelihood of patients experiencing a fracture according to BMD at baseline.

Over 2 years of treatment, the bisphosphonates did increase BMD by 3.6% relative to the observational group — not far short of the BMD increases of 4.2% seen in the parathyroidectomy group within the same time frame, compared with a reduction in BMD in those who underwent observation only.

Yet the bisphosphonates not only did not prevent fracture; there was evidence of harm, with increased fracture risk in both osteopenic and osteoporotic patients. In contrast, parathyroidectomy was associated with reduced fracture risk in both these populations.

Parathyroid Surgery the Best Option

The beneficial effect of parathyroidectomy on fracture risk "was concordant with short-term increases in BMD observed during the 2 to 5 years after surgery," Dr Yeh noted.

And parathyroid surgery was most protective in osteoporotic patients with regard to hip fracture.

Asked why an increase in BMD achieved with medical therapy with bisphosphonates didn't decrease fracture risk, Dr Yeh didn't have an adequate explanation, admitting that it remains a mystery.

"But we have to conclude that even though bones appear strong on BMD scanning, there is something wrong with the quality of the bone in patients treated with bisphosphonates. The bone could be dense but brittle," for example, he said.

He added: "Retrospective studies are never perfect, but right now, somewhere between 10% and 25% of people with primary hyperparathyroidism ever have parathyroid surgery, and for those who don't, they are going to fall down and fracture their hips unnecessarily, when we could do something small, easy, and cheap to prevent two-thirds of these fractures from occurring.

"So if our paper shows anything at all, it shows that there is really no viable alternative to parathyroid surgery. What we thought was an alternative is not acceptable," he concluded.

The study was funded by the National Institute on Aging, the Early Medical/Surgical Subspecialists' Transition to Aging Research, and its companion grant program, the American Geriatrics Society Jahnigen Career Development Award. Dr Yeh had no relevant financial relationships. Disclosures for the coauthors are listed in the article.

Ann Intern Med. Published online April 4, 2016. Abstract

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