What are renal osteodystrophy and dynamic bone disease in patients with chronic kidney disease (CKD), particularly those on dialysis or with a history of kidney transplantation?

Renal Osteodystrophy and Adynamic Bone Disease

Definition and Core Concepts

Renal osteodystrophy (ROD) refers specifically to alterations in bone morphology that occur as a direct consequence of chronic kidney disease, while adynamic bone disease represents one specific histologic pattern of ROD characterized by suppressed bone formation, low cellularity, and thin osteoid seams. 1

The term CKD-Mineral and Bone Disorder (CKD-MBD) describes the broader clinical syndrome encompassing abnormalities in bone and mineral metabolism and/or extraskeletal calcification that develops systemically due to CKD. 1 ROD is the skeletal component of this larger syndrome. 2

Renal Osteodystrophy: Pathophysiology and Classification

Underlying Mechanisms

ROD develops from a complex cascade of hormonal and metabolic disruptions:

• Phosphate retention occurs early in CKD, directly stimulating PTH secretion and triggering the pathophysiologic cascade. 3
• Elevated FGF-23 suppresses renal production of 1,25-dihydroxyvitamin D and is independently associated with mortality and vascular calcification. 3
• Decreased calcitriol production reduces intestinal calcium absorption, leading to hypocalcemia and further PTH elevation. 4
• Secondary hyperparathyroidism develops as a compensatory response, driving high-turnover bone disease with accelerated bone resorption. 3

Classification System

ROD is classified based on three parameters assessed by bone biopsy with histomorphometry: 1

• Turnover (high vs. low bone formation rate)
• Mineralization (normal vs. defective)
• Volume (normal, increased, or decreased bone mass)

The major histologic patterns include:

• High-turnover disease (osteitis fibrosa): Excessive PTH drives accelerated bone resorption and formation, releasing calcium and phosphate into circulation. 3 This was historically the most common form but has become less prevalent. 2
• Low-turnover disease (adynamic bone): Characterized by suppressed bone formation with low PTH levels, now the most common pattern in many dialysis centers. 2, 5
• Osteomalacia: Defective mineralization, historically associated with aluminum toxicity but now rare. 2
• Mixed uremic osteodystrophy: Features of both high and low turnover. 6

Adynamic Bone Disease: The Emerging Dominant Pattern

Definition and Prevalence

Adynamic bone disease has become increasingly prevalent since aggressive use of calcium-based phosphate binders and vitamin D analogs became standard practice, and now represents the most common bone disorder in many CKD populations. 2

The condition is characterized by: 2

• Suppressed bone formation and resorption
• Low cellularity
• Thin osteoid seams
• Typically associated with PTH levels <100 pg/mL, though can occur with PTH >400 pg/mL due to PTH assay limitations. 2

Pathogenesis

Multiple factors contribute to adynamic bone disease: 2

• Oversuppression of PTH from aggressive vitamin D therapy
• Chronic positive calcium balance from high-dose calcium-based phosphate binders
• Post-parathyroidectomy state
• Aging and diabetes mellitus, which independently predispose to osteoporosis
• Uremic toxins and metabolic derangements

Clinical Consequences: Not a Benign Condition

Accumulating evidence demonstrates that adynamic bone disease is not benign and carries significant clinical consequences. 2

Fracture Risk

• 4-fold increase in hip fracture risk compared to the general population. 2
• Increased vertebral collapse fractures associated with reduced bone density and low PTH values. 2
• Risk factors include age, duration of dialysis, female sex, and diabetes. 2

Impaired Mineral Homeostasis

The relatively inert adynamic bone cannot modulate calcium and phosphate levels appropriately: 2

• Minimal calcium loading leads to marked hypercalcemia because bone cannot take up calcium normally. 2
• Decreased calcium accretion despite similar intestinal absorption as high-turnover patients. 2
• Increased risk of metastatic calcification as calcium accumulates in soft tissues rather than bone. 2
• Calciphylaxis risk: Recent cases show association with low PTH and adynamic histology, contrasting with older descriptions linking it to hyperparathyroidism. 2

Diagnostic Approach

Low intact PTH levels (<100 pg/mL) strongly suggest adynamic bone disease, but PTH >400 pg/mL does not exclude it. 2

• Bone biopsy with histomorphometry remains the gold standard for definitive diagnosis, particularly when PTH levels are at or above target ranges. 2, 7
• Bone turnover markers (bone-specific alkaline phosphatase, P1NP) may assist in assessment but require further validation in CKD. 2
• DXA scanning can identify low bone density but cannot distinguish between adynamic bone and other forms of osteoporosis. 7, 5

Management Strategy

Treatment focuses on allowing PTH levels to rise to increase bone turnover. 2

This is accomplished by: 2

• Decreasing or eliminating calcium-based phosphate binders, particularly in patients with low PTH, hypercalcemia, or severe vascular calcification
• Reducing or stopping vitamin D analog therapy
• Switching to non-calcium-based phosphate binders (sevelamer, lanthanum) to minimize calcium loading

Critical pitfall: Attempting to normalize PTH to <65 pg/mL causes or worsens adynamic bone disease with increased vascular calcification risk. 3 Target PTH levels should be 200-300 pg/mL for CKD Stage 5 patients. 3

Post-Transplant Bone Disease

Changing Landscape

The nature of osteodystrophy prior to transplantation has fundamentally changed over the past decade, with more patients now osteopenic at transplant due to pre-existing adynamic bone disorder. 2

Historically, osteitis fibrosa and osteomalacia were the prevalent pretransplant bone diseases, and osteopenia was uncommon. 2 Now, adynamic bone disorder with osteopenia represents a significant component of bone disease at transplantation. 2

Post-Transplant Bone Loss

Rapid bone loss occurs in the early post-transplant period, with a nadir around 6 months, reaching 10% reduction at 12 months and 16% at 24 months. 2

The pathophysiology involves: 2

• Glucocorticoid therapy as the major factor, causing decreased osteoblast function and enhanced osteoclast activity
• Suppression of bone formation with marked decrease in mineral apposition rate
• Persistent hyperparathyroidism in some patients, predicting greater vertebral bone density loss
• Development of osteoporosis and adynamic bone disorder even in patients with pretransplant osteitis fibrosa

Fracture Burden

Fracture rates increase dramatically from 0.009 fractures per patient per year pre-transplant to 0.032 post-transplant. 2

• 10-15% of kidney transplant recipients sustain peripheral bone fractures. 2
• 10-15% sustain vertebral fractures. 2
• Vertebral bodies, ribs, and hips are most commonly affected. 2
• Fractures represent major obstacles to post-transplant rehabilitation and add tremendously to healthcare costs. 2

Monitoring and Management

DEXA is the clinical standard for measuring bone mineral density, and transplant recipients should be monitored regularly for bone mass changes. 2

• Monitor bone density every 6-12 months in the first 2 years post-transplant
• If osteoporosis is identified by BMD changes, initiate therapy promptly. 2
• Minimize glucocorticoid exposure when immunologically safe. 2
• Address persistent hyperparathyroidism, which is an independent fracture risk factor. 2

Relationship to Osteoporosis

While osteodystrophy and osteoporosis have traditionally been defined as distinct entities, they likely coexist in kidney failure (Stage 5 CKD). 2

The 2025 KDIGO Controversies Conference introduced the term "CKD-associated osteoporosis" as an inclusive definition recognizing the global impact of kidney disease on bone strength. 2 This acknowledges that:

• Many risk factors for adynamic bone disease (aging, diabetes, immobility) also predispose to osteoporosis in the general population. 2
• Low bone turnover characterizes both adynamic bone disease and most osteoporosis in non-CKD patients. 2
• The aging dialysis population faces high osteoporosis risk independent of uremia. 2
• Fracture risk in CKD exceeds that explained by bone density alone, indicating bone quality defects. 7, 5

Clinical Implications and Monitoring

Laboratory Assessment

For CKD Stage 4, measure every 3 months: 3

• PTH (target 70-110 pg/mL)
• Calcium
• Phosphorus

For CKD Stage 5, measure monthly initially, then every 3 months once stable: 3

• PTH (target 200-300 pg/mL)
• Calcium
• Phosphorus
• Consider bone turnover markers (bone-specific alkaline phosphatase)

Key Management Principles

Phosphorus control is the cornerstone of preventing ROD progression. 3

• Target phosphorus 2.7-4.6 mg/dL for Stage 4,3.5-5.5 mg/dL for Stage 5. 3
• Dietary phosphorus restriction to 800-1,000 mg/day when PTH rises above target. 3
• Prefer non-calcium-based binders in patients with low PTH, hypercalcemia, or vascular calcification. 3

Avoid PTH oversuppression. 2, 3

• Do NOT attempt to normalize PTH to general population ranges
• Recognize that very low PTH (<100 pg/mL) indicates adynamic bone risk
• Reduce calcium and vitamin D therapy if PTH falls below target

Monitor for complications. 2

• Screen for fractures, particularly in high-risk patients (elderly, diabetic, female, long dialysis vintage)
• Assess for vascular calcification
• Watch for hypercalcemia episodes suggesting adynamic bone