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

Area of Science:

• Endocrinology
• Metabolic Bone Disease
• Calcium Homeostasis

Background:

• Normocalcemic hyperparathyroidism (NCHPTH) presents with elevated parathyroid hormone (PTH) and normal calcium levels, excluding secondary causes.
• NCHPTH is frequently underdiagnosed and associated with significant bone compromise, including osteoporosis and fragility fractures.
• This study investigated NCHPTH within a dedicated Metabolic Bone Disease Service (MBDS).

Purpose of the Study:

• To prospectively investigate the prevalence and characteristics of NCHPTH in patients referred to an MBDS.
• To assess the association between NCHPTH and skeletal pathology.
• To evaluate diagnostic strategies for NCHPTH.

Main Methods:

• A prospective observational cohort study included 815 patients referred to the MBDS with osteoporosis diagnoses.
• Patients underwent dual-energy X-ray absorptiometry (DXA) and biochemical assays including serum calcium, 25-hydroxy-vitamin D (25[OH]D), and PTH.
• Diagnostic criteria for NCHPTH involved normal serum calcium with elevated PTH, after excluding secondary causes.

Main Results:

• NCHPTH was identified in 3% of referred patients (25 individuals), with a high prevalence of skeletal involvement (72% with prior fragility fractures).
• Mean PTH levels were elevated (130.8 pg/mL) while serum calcium and 25(OH)D remained within normal ranges.
• The MBDS showed a higher prevalence of NCHPTH compared to other referral populations, likely due to the focus on skeletal compromise.

Conclusions:

• NCHPTH is frequently associated with substantial skeletal pathology, not just biochemical abnormalities.
• Relying solely on serum calcium levels can lead to underdiagnosis of NCHPTH.
• Routine PTH testing is crucial for earlier NCHPTH detection, enabling timely interventions and improving secondary fracture prevention.