EC Orthopaedics

Review Article Volume 16 Issue 7 - 2025

Vitamin D in the Endocrine Circuit: Focus on Interactions Between Vitamin D, PTH and Leptin

Rosini Sergio1, Saviola Giannantonio2, Stefano Rosini3, Molfetta Francesco4 and Molfetta Luigi5*

1Biomaterial Research Center, Livorno, Italy

2Istituti Clinici Scientifici Maugeri, IRCCS Castel Goffredo, Castel Goffredo, Italy

3Smile-Restyle, Livorno, Italy

4DINOGMI Department, School of Medical and Pharmaceutical Sciences, Research Center of Osteoporosis and Osteoarticular Pathologies, University of Genoa, Genoa, Italy

5DISC Department, School of Medical and Pharmaceutical Sciences, Research Center of Osteoporosis and Osteoarticular Pathologies, University of Genoa, Genoa, Italy

*Corresponding Author: Molfetta Luigi, Professor, DISC Department, School of Medical and Pharmaceutical Sciences, Research Center of Osteoporosis and Osteoarticular Pathologies, University of Genoa, Genoa, Italy.
Received: October 23, 2025; Published: November 28, 2025




Vitamin D (Vit D) plays a central role in calcium-phosphate homeostasis and bone health, but its pleiotropic actions extend far beyond skeletal physiology. Increasing evidence indicates a complex interplay between Vit D status, obesity, leptin signaling, and parathyroid hormone (PTH) regulation. Low serum 25-hydroxyvitamin D (25OHD) is frequently associated with obesity, yet this relationship cannot be fully explained by sequestration of Vit D in adipose tissue. Instead, adipocyte-derived leptin and fibroblast growth factor 23 (FGF23) emerge as key mediators modulating parathyroid function and Vit D metabolism. Studies demonstrate that PTH levels in obese individuals correlate more strongly with leptin than with 25OHD, while calcium exerts only a modest influence. Leptin appears to act directly on the parathyroid glands, promoting hypertrophy and inhibiting CaSR activity, while simultaneously inducing osteocytic FGF23 expression, which suppresses renal 1α-hydroxylase (CYP27B1) and decreases calcitriol synthesis. These mechanisms contribute to secondary hyperparathyroidism in obesity, independent of Vitamin D deficiency per se. Furthermore, leptin resistance may disrupt hormonal feedback loops, altering energy metabolism and osteoblast activity. Meta-analyses suggest that approximately 1000 IU/day of Vit D supplementation is sufficient to lower PTH in most individuals, though higher doses primarily increase serum 25OHD without further suppressing PTH. However, obese patients typically require larger doses, not only due to altered Vit D distribution but also because of leptin- and FGF23-mediated inhibition of Vit D activation. Calcium intake remains a critical determinant of PTH regulation, particularly in individuals with normal BMI, whereas in obese subjects the combined effects of calcium, Vit D, and leptin must be considered.

In conclusion, the relationship between Vit D, obesity, leptin, and PTH is multifactorial and highly variable across individuals. No universal Vit D dose can be recommended. Instead, personalized supplementation strategies should be adopted, taking into account BMI, leptin levels, calcium intake, age, genetic factors, and comorbidities, to optimize skeletal and metabolic outcomes.

 Keywords: Vitamin D; Parathyroid Hormone; Leptin; FGF23; Obesity; Calcium Metabolism

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Molfetta Luigi., et al. “Vitamin D in the Endocrine Circuit: Focus on Interactions Between Vitamin D, PTH and Leptin”. EC Orthopaedics  16.7 (2025): 01-07.

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