CKD and Calcium: Key Effects on Bone Health

Chronic kidney disease (CKD) affects multiple systems in the body, with bone health being a major concern. The kidneys regulate mineral balance, and when their function declines, disruptions in calcium levels weaken bones, increasing the risk of fractures and other complications.

Understanding how CKD influences calcium regulation is essential for managing its impact on bone strength.

Calcium Homeostasis In Renal Function

The kidneys regulate calcium balance through filtration, reabsorption, and excretion, ensuring serum levels stay within a narrow range. Under normal conditions, about 99% of the calcium filtered by the glomeruli is reabsorbed along the nephron, primarily in the proximal tubule, loop of Henle, and distal convoluted tubule. This prevents excessive calcium loss while maintaining levels necessary for neuromuscular activity and bone mineralization.

Renal calcium handling responds to systemic signals that dictate whether calcium should be conserved or excreted. The proximal tubule passively reabsorbs around 65% of filtered calcium, following sodium and water movement. The loop of Henle, particularly the thick ascending limb, accounts for another 20–25% through paracellular transport mechanisms. The distal convoluted and connecting tubules reclaim the remaining 5–10% under tight hormonal control, allowing precise adjustments in calcium reabsorption. These segments are particularly sensitive to regulatory factors that modulate calcium transport proteins, such as transient receptor potential vanilloid 5 (TRPV5) channels and calbindin-D28k, which facilitate calcium entry and intracellular movement.

The kidneys also influence calcium homeostasis by modulating phosphate excretion, which indirectly affects calcium availability. Phosphate and calcium share an inverse relationship in serum, meaning disruptions in phosphate handling can lead to imbalances in calcium levels. When renal function declines, phosphate retention alters calcium-phosphate interactions, contributing to pathological mineral deposition. This underscores the kidneys’ role in maintaining overall mineral equilibrium necessary for skeletal and systemic health.

Hormonal Regulation

Calcium regulation is controlled by a network of hormones that respond dynamically to mineral level fluctuations. Parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and calcitriol (active vitamin D) are the primary regulators, modulating intestinal absorption, renal reabsorption, and skeletal mobilization. In CKD, the interplay between these hormones becomes dysregulated, leading to significant alterations in calcium balance and bone integrity.

PTH plays a central role by responding to decreases in serum calcium. Secreted by the parathyroid glands, it stimulates calcium release from bone, enhances renal calcium reabsorption, and promotes calcitriol production in the kidneys. Calcitriol, in turn, facilitates intestinal calcium absorption. In CKD, impaired renal function reduces calcitriol production, leading to diminished calcium absorption and persistent hypocalcemia. This triggers sustained PTH secretion, known as secondary hyperparathyroidism, which accelerates bone resorption and contributes to skeletal fragility.

FGF23, primarily secreted by osteocytes in response to elevated phosphate, enhances phosphate excretion while suppressing calcitriol synthesis. In CKD, phosphate retention leads to excessive FGF23 production, disrupting vitamin D metabolism and indirectly affecting calcium handling. Elevated FGF23 levels impair osteoblast function and reduce bone mineralization, compounding the effects of secondary hyperparathyroidism and worsening skeletal complications.

Possible Shifts In Calcium Levels In CKD

As kidney function declines, calcium regulation becomes increasingly compromised. One of the earliest disturbances is reduced calcium absorption in the gut due to impaired vitamin D activation. The kidneys convert 25-hydroxyvitamin D into calcitriol, the active form necessary for efficient intestinal calcium uptake. When this conversion diminishes, dietary calcium absorption drops, leading to persistent hypocalcemia. This deficiency may go unnoticed in early CKD stages but progressively worsens, prompting compensatory mechanisms that disrupt mineral balance.

In response to falling calcium levels, the parathyroid glands intensify PTH secretion, increasing calcium mobilization from bone and enhancing renal calcium reabsorption. While this initially stabilizes calcium concentrations, prolonged PTH elevation accelerates bone turnover, weakening skeletal structures. PTH-driven calcium release from bone is not always sufficient to offset reduced intestinal absorption, leading to fluctuating calcium levels. Some patients experience transient normocalcemia, while others remain chronically deficient despite elevated PTH.

As CKD advances, impaired phosphate excretion leads to phosphate accumulation in the bloodstream. Excess phosphate binds to circulating calcium, forming insoluble complexes that further lower free calcium concentrations. This process exacerbates hypocalcemia and increases vascular calcification risk. The deposition of calcium-phosphate complexes in blood vessels and soft tissues diverts calcium away from physiological processes, creating a paradox where total body calcium may be elevated, yet bioavailable calcium remains insufficient for normal functions.

Bone And Mineral Relationship

Bone health depends on balanced mineral levels, with calcium serving as the primary structural component. Bones act as a dynamic reservoir, continuously remodeling through the coordinated activity of osteoclasts, which break down bone tissue, and osteoblasts, which promote mineral deposition. This remodeling ensures resilience and adaptation to mechanical stress. In CKD, progressive mineral dysregulation accelerates bone loss and impairs remodeling, increasing fracture risk.

Phosphate also plays a significant role in bone integrity. While necessary for hydroxyapatite formation—the mineralized component that gives bones hardness—excess phosphate, common in CKD, disrupts mineralization. Phosphate retention can cause osteomalacia, characterized by defective bone mineralization and structural weakness. Conversely, unchecked phosphate accumulation can drive extraskeletal calcification, where minerals deposit in blood vessels and soft tissues instead of bone. These changes not only compromise skeletal strength but also contribute to cardiovascular complications, further complicating disease management.