What are the roles of Vitamin D and Parathyroid Hormone (PTH) in the body?

Roles of Vitamin D and Parathyroid Hormone (PTH) in the Body

Vitamin D and PTH work together in a tightly regulated feedback system to maintain calcium and phosphate homeostasis, which is critical for bone health, cardiovascular function, and overall mortality outcomes.

Vitamin D Functions

• Vitamin D is synthesized in the skin during sun exposure or obtained from food, then undergoes hydroxylation in the liver to 25-hydroxyvitamin D (25(OH)D) and in the kidney to its active form, 1,25-dihydroxyvitamin D (1,25(OH)2D or calcitriol) 1
• The active form of vitamin D facilitates intestinal calcium absorption by binding to vitamin D receptors and stimulating the production of calcium binding proteins 2, 1
• Vitamin D maintains adequate levels of calcium and phosphate for proper bone mineralization and prevention of conditions like rickets and osteomalacia 1
• In chronic kidney disease (CKD), vitamin D supplementation helps control secondary hyperparathyroidism, which is associated with CKD progression, cardiovascular events, mortality, and fractures 3
• Vitamin D has been shown to reduce inflammation, improve endothelial function, and control secretion of insulin 3

PTH Functions

• PTH is primarily regulated by serum ionized calcium levels - low calcium stimulates PTH secretion while high calcium suppresses it 4
• PTH increases calcium reabsorption in the kidney while simultaneously decreasing phosphate reabsorption (phosphaturic effect), leading to increased urinary phosphate excretion 5
• PTH stimulates the conversion of 25(OH)D to 1,25(OH)2D in the kidney, enhancing intestinal calcium absorption 5
• PTH stimulates bone resorption to release calcium into the bloodstream when serum calcium levels are low 4
• The phosphaturic effect of PTH is critical for maintaining normal serum phosphate levels, especially in early stages of kidney disease 5

Vitamin D and PTH Interrelationship

• PTH and vitamin D form a tightly controlled feedback cycle - PTH stimulates vitamin D synthesis in the kidney while vitamin D exerts negative feedback on PTH secretion 4
• There is a negative relationship between serum 25(OH)D and serum PTH levels - when vitamin D levels decrease below approximately 75 nmol/L (30 ng/mL), PTH levels begin to rise 1
• Vitamin D deficiency leads to decreased intestinal calcium absorption, resulting in hypocalcemia which stimulates PTH secretion, leading to secondary hyperparathyroidism 6
• In CKD, reduced kidney function impairs the conversion of 25(OH)D to 1,25(OH)2D, contributing to secondary hyperparathyroidism 3

Clinical Implications

• Maintaining adequate vitamin D levels (≥30 ng/mL or 75 nmol/L) is important for bone health and may reduce fracture risk 3
• In CKD patients, the optimal PTH level remains undefined, but high and progressively increasing PTH levels warrant investigation 3
• For patients on dialysis with serum intact PTH levels >300 pg/mL, active vitamin D sterols are recommended to reduce PTH to a target range of 150-300 pg/mL 3
• Vitamin D supplementation in vitamin D-deficient individuals can suppress elevated PTH levels, increase bone mineral density, and potentially decrease fracture risk 1
• Both vitamin D deficiency and elevated PTH have been associated with increased cardiovascular risk 3, 4

Special Considerations in CKD

• In CKD, the complex interplay between vitamin D and PTH is further complicated by impaired kidney function 3
• As kidney function declines, the phosphaturic effect of PTH becomes increasingly important but eventually reaches its maximum effect when creatinine clearance falls below 20-30 mL/min/1.73 m² 5
• In CKD patients, maintaining calcium and phosphate at adequate levels is important for bone health - hypocalcemia stimulates PTH and favors mineralization defects, while hypercalcemia suppresses PTH 3
• The concept of a "pleiotropic" effect for vitamin D should be abandoned, but low-dose active vitamin D could help control PTH when used with nutritional vitamin D and dietary phosphate restriction 3

Monitoring and Management

• For patients treated with vitamin D sterols, serum calcium and phosphorus should be monitored at least every 2 weeks for 1 month and then monthly thereafter 3
• PTH should be measured monthly for at least 3 months and then every 3 months once target levels are achieved 3
• Management should integrate changes in serum calcium, phosphorus, and PTH levels 3
• In patients with vitamin D deficiency, supplementation should be considered to maintain adequate levels, particularly in those at risk for bone disease 3