Positive effect of parathyroidectomy compared to observation on BMD in a randomized controlled trial of mild primary hyperparathyroidism.

Mild or asymptomatic disease is now the dominating presentation of primary hyperparathyroidism (PHPT). However, bone involvement with decreased bone mineral density (BMD) and an increased risk of fractures has been demonstrated. Indications for parathyroidectomy (PTX) in mild PHPT have been debated for years. There is a need of long-term randomized studies comparing PTX with observation without intervention (OBS). Here, we present bone health data from the Scandinavian Investigation of Primary Hyperparathyroidsm (SIPH), a randomized controlled trial, comparing PTX to OBS. This study included 191 patients (96 OBS/95 PTX), and 129 patients (64 OBS/65 PTX) were followed for 10 years, to the End-of-Study (EOS). BMD was measured with dual-energy x-ray absorptiometry (DXA), peripheral fractures were noted and spine radiographs were obtained for vertebral fracture assessment. There was a significant treatment effect of PTX on BMD, as compared to OBS, for all analyzed compartments, most explicit for the lumbar spine (LS) and femoral neck (FN) (P<0.001). The mean changes in T-score from baseline to 10 years were from 0.41 for radius 33% (Rad33) to 0.58 for LS greater in the PTX group than in the OBS group. There was a significant decrease in BMD for all compartments in the OBS group, most pronounced for FN, Rad33 and ultradistal radius (UDR) (P<0.001). Even though there was a significant treatment effect of PTX as compared to OBS, there was only a significant increase in BMD over time for LS (P<0.001). We found no difference between groups in fracture frequency in the 10-year cohort, neither with modified intention to treat (mITT) analysis nor per protocol analysis. As BMD is only a surrogate endpoint of bone health and PTX did not reduce fracture risk, observation could be considered a safe option for many patients with mild PHPT regarding bone health in a 10-year perspective.