Simple SummaryPatients undergoing medical treatment for mild pHPT maintain higher calcium and PTH levels. Patients managed medically had worse BMD outcomes. Considering this, and the superior biochemical and musculoskeletal outcomes which our study elucidates, we recommend that parathyroidectomy should be considered a superior treatment option compared to medical management for most patients with mild pHPT.AbstractBackground: Parathyroidectomy is the definitive cure for patients with primary hyperparathyroidism (pHPT) and has an annual prevalence of 0.2–1% in the United States. Some patients with mild disease are medically managed effectively using calcium-lowering medications and drugs against complications such as osteoporosis; however, many maintain a persistently high calcium level that negatively impacts their skeletal, renal, and psychogenic systems over the long term. This meta-analysis aims to compare the outcomes of medical management versus parathyroidectomy in patients with mild pHPT. Study Design: This meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using PubMed, Embase, and Web of Science by two teams of investigators. Analysis was run using R packages. Results: A total of 12 publications including seven randomized control, two prospective, and three retrospective trials with a total of 1346 patients were included for analysis. The average follow-up for all patients was 41 ± 23.8 months. Demographics, pre-treatment calcium, PTH, and bone mineral density (BMD) were similar between the medical (N= 632) and surgical (N= 714) cohorts. Post-treatment calcium and PTH levels were significantly higher in the medical cohort (10.46 vs. 9.39,p< 0.01), (106.14 vs. 43.25,p= 0.001), respectively. Interestingly, the post-treatment PTH in the medical cohort increased when compared to pre-treatment (83.84 to 106.14). Patients in the medical cohort had lower BMD in lumbar (0.48 g/cm2; OR = 0.42, 95% CI = 0.21, 0.83), femoral (0.48; OR = 0.42, 95% CI = 0.29, 0.61), and hip (0.61; OR = 0.33, 95% CI = 0.13, 0.85). Incidences of fracture, nephrolithiasis, cardiovascular death, or overall mortality were not significantly different between the cohorts. Conclusions: The present study is the most comprehensive meta-analysis on mild pHPT to date. Our findings reflect that parathyroidectomy is the superior option in the treatment of mild pHPT patients as opposed to medical management.