Effects of Normocalcemic Hyperparathyroidism on Structural Bone Compromise: A Prospective Observational Cohort Study

Normocalcemic hyperparathyroidism (NCHPTH) is characterized by elevated serum parathyroid hormone (PTH) levels in the presence of normal serum calcium levels, with the exclusion of secondary causes. NCHPTH remains underdiagnosed and is often associated with structural compromise of bone, namely osteoporosis and fragility fractures. The purpose of this study was to perform a prospective observational cohort study investigating NCHPTH in our Metabolic Bone Disease Service (MBDS).

Between January 2022 and June 2024, 815 patients were referred to our MBDS with an International Classification of Diseases, Tenth Revision diagnosis code of osteoporosis. Each patient underwent dual energy X-ray absorptiometry, and when indicated, assays for serum calcium, ionized calcium, 25-hydroxy-vitamin D (25[OH]D), and PTH.

NCHPTH was identified in 25 patients (3%), approximating one patient per month. Skeletal involvement was frequent in the NCHPTH cohort, with 72% presenting with a history of fragility fractures. Mean PTH levels were 130.8 pg/mL, while serum calcium and 25(OH)D levels remained within the normal range. We compared the prevalence of NCHPTH in our MBDS to other referral populations, finding an increased prevalence in our service, likely due to the high frequency of skeletal compromise in this population.

These results indicate that NCHPTH is not merely a biochemical phenomenon but is rather frequently associated with skeletal pathology. We conclude that reliance on serum calcium alone likely leads to underdiagnosis of NCHPTH, whereas routine PTH testing can facilitate earlier detection, allow for preventative interventions, and enhance secondary fracture prevention efforts.