Serum PTH ≥ 40 pg/mL as a Marker of Bone Fragility and Vitamin D Deficiency in Periodontitis Patients: Biochemical, Densitometric and Genetic Evidence

(1) Background: this study aimed to determine whether a serum parathyroid hormone (PTH) threshold of 40 pg/mL represents a clinically relevant risk factor for vitamin D (VitD) deficiency and reduced bone mineral density (BMD). It also investigated potential genetic interactions influencing PTH regulation and skeletal health in patients with periodontitis. (2) Methods: a cross-sectional analysis was conducted on 1038 periodontitis patients (35-75 years). Serum PTH, VitD, calcium (Ca), phosphate (P), and urinary parameters were assessed. Dual-energy X-ray absorptiometry (DXA) was used to evaluate BMD in 261 subjects. Vitamin D Receptor (VDR) and estrogen receptor alpha (ERα) polymorphisms were genotyped, and composite genetic risk scores were calculated. Statistical analyses included correlation tests, subgroup comparisons, and regression models. (3) Results: sixty-two percent of individuals had PTH > 40 pg/mL, which was associated with significantly lower 25(OH)D and Ca levels and reduced T-scores (<i>p</i> < 0.05). PTH levels negatively correlated with BMD (Pearson's r = -0.159, <i>p</i> = 0.0105). Patients with higher ERα polymorphism scores showed increased PTH values (<i>p</i> < 0.05), while VDR variants demonstrated a positive but no significant trend. (4) Conclusions: a PTH threshold of 40 pg/mL identifies individuals at higher risk of VitD deficiency and skeletal fragility, even without overt hypercalcemia. Genetic factors, particularly ERα variants, may contribute to elevated PTH levels, suggesting value in integrating biochemical, densitometric, and genetic screening for early bone health risk stratification.