OVERVIEW OF RENAL OSTEODYSTROPHY
- Definition: Refers to bone morphology alterations found in patients with chronic kidney disease (CKD).
- Common Forms:
- High bone turnover due to secondary or tertiary hyperparathyroidism (HPT), including osteitis fibrosa cystica
- Low bone turnover with adynamic bone disease
- Low bone turnover combined with increased unmineralized bone (osteomalacia)
- β₂-microglobulin–associated amyloid deposits forming bone cysts
- Mixed osteodystrophy with both high- and low-turnover elements
TWO KEY PATHOLOGIC FACTORS IN CKD
- Decreased Renal Conversion of 25(OH)D → 1,25(OH)₂D (calcitriol)
- Decreased Ability to Excrete Inorganic Phosphate (Pi)
SECONDARY HYPERPARATHYROIDISM (HPT)
- As GFR decreases, the filtered load of phosphate falls → serum phosphate rises → serum calcium (Ca²⁺) drops → PTH increases (secondary HPT).
- Also, reduced 1,25(OH)₂D production (due to decreased renal mass) → less calcium absorbed from gut → further PTH rise.
- Although initially PTH partially corrects these abnormalities (by lowering phosphate reabsorption, raising bone resorption of calcium, and boosting calcitriol), over time it becomes maladaptive as kidney function worsens.
TERTIARY HYPERPARATHYROIDISM
- Definition: Refractory hypersecretion of PTH with severe parathyroid hyperplasia or neoplastic transformation (monoclonal adenomas).
- Pathophysiology:
- Failing kidneys can’t excrete phosphate despite high PTH → continued bone resorption elevates both calcium + phosphate → hypercalcemia → metastatic calcification (soft tissues, joints, arteries) → can cause ischemia, gangrene.
- Bone Findings: Subperiosteal resorption, cysts, osteitis fibrosa cystica (brown tumors), fractures, “salt-and-pepper” skull, “band” vertebral sclerosis.
ADYNAMIC BONE DISEASE
- Most common in dialysis patients (peritoneal or hemodialysis).
- Low bone turnover, absence of bone cell activity → no osteoid formation increase (unlike osteomalacia).
- Associated with excess PTH suppression (e.g., due to calcium-based phosphate binders and vitamin D analogues).
- Clinical: Raises fracture risk (e.g., hip fractures).
- Biochemical Clue: Often serum PTH <100 pg/mL.
- Key Management: Allow PTH to rise by reducing or discontinuing calcium-based binders / vitamin D analogues.
OSTEOMALACIA (WITH RENAL FAILURE)
- Pathophysiology: Decreased bone turnover + excess unmineralized bone, from vitamin D deficiency or aluminum intoxication.
- Radiographic Findings:
- Looser zones (pseudofractures) = narrow radiolucent lines, perpendicular to cortex, with sclerotic borders; bilateral and symmetric.
- Bone resorption at lateral clavicle ends.
- Milkman syndrome = bilateral symmetric pseudofractures in osteomalacia.
- Fractures: Minimal or no trauma, commonly in long bones (e.g., hip), ribs, vertebrae.
- Diagnostic: Bone biopsy after tetracycline labeling can confirm decreased mineralization.
OTHER FACTORS CONTRIBUTING TO BONE DISEASE IN CKD
- Vitamin K deficiency (needed for bone matrix protein carboxylation).
- Bone morphogenetic protein-7 deficiency (kidney normally produces BMP-7 to aid osteoblast differentiation).
TREATMENT APPROACHES
- Normalize serum Ca²⁺ and phosphate levels while minimizing aluminum.
- Dietary phosphate restriction plus phosphate binders if GFR <25% normal.
- Vitamin D supplementation to maintain normal 1,25(OH)₂D levels.
- Parathyroidectomy for tertiary HPT or intractable secondary HPT with severe hypercalcemia / bone disease.