Parathyroidectomy does not lower fracture rates for adults with mild hyperparathyroidism
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Adults with mild hyperparathyroidism who underwent a parathyroidectomy did not have a difference in fracture events at 10 years compared with adults who did not undergo surgery, according to study data.
In findings from a randomized controlled trial published in The Journal of Bone and Mineral Research, adults who underwent a parathyroidectomy had significantly greater bone mineral density increases 10 years after the procedure compared with adults who underwent observation without surgery. However, only lumbar spine BMD in the surgical group was significantly increased over time compared with baseline, and the rate of fractures in the two groups was not significantly different at 10 years.
“As fracture outcome is a hard endpoint with relevance for the patient, observation of patients with mild hyperparathyroidism can be considered safe in a 10-year perspective, with no proven practical bone health benefits of parathyroidectomy,” Karolina Lundstam, MD, a research student in the department of radiology, Institute of Clinical Sciences at The Sahlgrenska Academy at the University of Gothenburg in Sweden, and colleagues wrote.
Researchers conducted a randomized controlled trial in Denmark, Sweden and Norway in which 191 adults aged 50 to 80 years with mild hypoparathyroidism were randomly assigned to undergo a parathyroidectomy or observation without intervention between 1998 and 2005. Of the study cohort, 129 adults completed a 10-year follow-up visit, including 65 in the parathyroidectomy group and 64 in the observation group. Calcium, albumin and parathyroid hormones were measured annually. DXA scans were performed at baseline, 5 years and 10 years. New fractures occurring during the 10-year follow-up were analyzed.
Albumin-corrected calcium decreased in both groups during the study. Parathyroid hormone levels decreased only in the surgery group from baseline to 10 years (mean difference, –4.64 pmol/L; P < .001), with no difference in the observation group.
Compared with the observation group, greater BMD T-score increases were found at 10 years in the parathyroidectomy group at all analyzed areas, with the largest differences observed at the lumbar spine and femoral neck. Compared with baseline, the observation group had BMD T-score decreases in all analyzed areas, whereas the parathyroidectomy group had significant BMD T-score decreases in the forearm from baseline to 10 years. The only area where BMD T-scores increased in the parathyroidectomy group from baseline to 10 years was at the lumbar spine.
Of those who completed the 10-year follow-up, 32.8% in the observation group and 28.1% in the parathyroidectomy group sustained a fracture. No difference in fracture events was observed between the groups using modified intention-to-treat analysis. There was also no difference in fractures using per-protocol analysis in which participants in the observation group who underwent a parathyroidectomy during the follow-up period were excluded.
The researchers noted that there may have been a lower-than-expected number of fractures due to the age of the cohort. Of the fractures reported in the study, only one was a hip fracture.
“One can assume that more patients in our study population will suffer from hip fractures in the future,” the researchers wrote. “The overall fracture incidence increases with age and with the BMD difference between parathyroidectomy and observation without intervention seemingly increasing with time, a future difference in fracture events cannot be ruled out.”
Perspective
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In resource rich countries where routine multichannel laboratory testing includes serum calcium, primary hyperparathyroidism is diagnosed in patients with mild or no symptoms. Surgery is recommended for patients younger than age 50 years and for patients with clinically significant hypercalcemia, osteoporosis or a fragility fracture, renal calculi or impaired renal function. Skeletal health is a frequent concern in hyperparathyroidism as excess parathyroid hormone increases bone turnover, and studies have shown decreased bone density over time. Bone density improves in patients undergoing parathyroidectomy, and some studies have also shown a decrease in fracture risk.
In this randomized controlled study, 191 adults aged 50 to 80 years with mild hyperparathyroidism, were assigned to parathyroidectomy or observation, and were followed for 10 years. Compared with the observation group, improvement in bone density was greater in the parathyroidectomy group at all analyzed sites, but this did not translate into a lower risk for fractures in the surgical group. The authors concluded that patients with mild hyperparathyroidism can safely be observed without surgery, as there was no reduction in risk of fractures with parathyroidectomy.
The number of fractures in this study was low, and this was partly due to the inclusion of younger patients. In addition, both arms of the study allowed for bisphosphonate use, which was higher in the observation group, which could have accounted for fracture reduction in this group, although the number of bisphosphonate-treated patients was low. Bone density did continue to decline in the observation group, which has long-term implications for patients already at risk for osteoporosis, such as postmenopausal women.
This study provides reassurance that as related to fracture risk, observation is safe for patients with asymptomatic, mild hyperparathyroidism, as parathyroidectomy may not be either possible or affordable in all regions of the world.
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