Even though new vertebral fractures occurred only in the observation group, the frequency was not significantly different from the surgery group. Longer follow-up is needed before firm conclusions can be drawn about the long-term safety of observation, as opposed to surgery.

Mild primary hyperparathyroidism (PHPT) is known to affect the skeleton, even though patients usually are asymptomatic. Treatment strategies have been widely discussed. However, long-term randomized studies comparing parathyroidectomy to observation are lacking. The objective was to study the effect of parathyroidectomy (PTX) compared with observation (OBS) on bone mineral density (BMD) in g/cm and T-scores and on biochemical markers of bone turnover (P1NP and CTX-1) in a prospective randomized controlled study of patients with mild PHPT after 5 years of follow-up. Of 191 patients with mild PHPT randomized to either PTX or OBS, 145 patients remained for analysis after 5 years (110 with validated DXA scans). A significant decrease in P1NP (p < 0.001) and CTX-1 (p < 0.001) was found in the PTX group only. A significant positive treatment effect of surgery compared with observation on BMD (g/cm ) was found for the lumbar spine (LS) (p = 0.011), the femoral neck (FN) (p < 0.001), the ultradistal radius (UDR) (p = 0.042), and for the total body (TB) (p < 0.001) but not for the radius 33% (Rad33), where BMD decreased significantly also in the PTX group (p = 0.012). However, compared with baseline values, there was no significant BMD increase in the PTX group, except for the lumbar spine. In the OBS group, there was a significant decrease in BMD (g/cm ) for all compartments (FN, p < 0.001; Rad33, p = 0.001; UDR, p = 0.006; TB, p < 0.001) with the exception of the LS, where BMD was stable. In conclusion, parathyroidectomy improves BMD and observation leads to a small but statistically significant decrease in BMD after 5 years. Thus, bone health appears to be a clinical concern with long-term observation in patients with mild PHPT. © 2017 American Society for Bone and Mineral Research.

Primary hyperparathyroidism (PHPT) was previously considered a disease presenting with multiorgan involvement and a wide range of symptoms. Today, the disease presents with no symptoms or mild symptomatology in most patients. Data regarding nonspecific symptoms such as pain, fatigue, memory loss, depression, and other neuropsychiatric signs have been ambiguous, and results from prospective long‐term randomized control trials are lacking. The Scandinavian Investigation on Primary Hyperparathyroidism (SIPH) is a prospective randomized controlled trial (RCT) with 10‐year follow up, comparing parathyroidectomy (PTX) to observation without any treatment (OBS). From 1998 to 2005, 191 patients with mild PHPT were included from Sweden, Norway, and Denmark. A total of 95 patients were randomized to PTX and 96 to OBS. The generic Short Form‐36 survey (SF‐36) and the Comprehensive Psychopathological Rating Scale (CPRS) were studied at baseline, 2, 5, and 10 years after randomization. After 10 years, the PTX group scored significantly better on vitality (PTX 65.1 ± 20.2 versus OBS 57.4 ± 22.7; p = .017) compared to the OBS group in SF‐36. We found no differences between the groups in the physical subscales. The OBS group had no significant change in any of the SF‐36 scores throughout the study. The CPRS showed an improvement of symptoms in both groups for single items and sum scores after 10 years compared to baseline. There were, however, no significant differences between the two groups in the CPRS data. The results of this large and long‐term RCT indicate improvement in some of the mental domains of SF‐36 following PTX. However, the treatment effects between the groups were subtle with uncertain clinical significance. The observation group had stable SF‐36 values and improvement in CPRS symptom‐scores. Thus, in considering only quality of life (QoL) and in the absence of declines in renal and skeletal parameters, it may be safe to observe patients with mild PHPT for a decade. © 2020 American Society for Bone and Mineral Research (ASBMR).