What is metabolic bone disease?

Metabolic Bone Disease: Definition and Overview

Metabolic bone disease (MBD) refers to a group of disorders characterized by abnormalities in bone metabolism, structure, or mineralization that negatively impact overall health and quality of life, placing individuals at high risk for fracture with increased morbidity and mortality. 1

Types of Metabolic Bone Disease

• Metabolic bone diseases encompass several distinct conditions that result in aberrant bone mineral homeostasis with resulting skeletal disease, ranging from nutritional deficiencies to genetic variants in skeletal genes 2

• The most common types include:

  • Renal osteodystrophy (ROD) - bone disorder associated with chronic kidney disease (CKD) 3
  • Osteoporosis - defined as a T-score ≤ -2.5 measured by DXA and/or having a fragility fracture at any level of bone mineral density 3
  • Osteomalacia - characterized by defective mineralization of osteoid 3
  • Adynamic bone disease - characterized by suppressed bone formation with various degrees of bone resorption 3
  • Mixed uremic osteodystrophy - with various degrees of mineralization defect and hyperparathyroid bone changes 3

Pathophysiology

• Bone strength is determined by bone quantity (mass), geometry (size, shape), microarchitecture (trabecular and cortical), and tissue properties (turnover, mineralization, collagen content, and microcracks) 3

• Abnormality in any of these features increases the risk of fractures 3

• In CKD, disturbed mineral metabolism is an important driver of bone disease, with hyperparathyroidism and vitamin D deficiency playing central roles 3

• Parameters of mineral metabolism (calcium, phosphate, 25-[OH]D, PTH, and FGF23) associate with bone disease and fracture risk 3

• High PTH may increase bone formation and resorption, resulting in impairments to bone quality, including cortical microarchitectural deterioration, abnormal bone mineralization, and altered crystal structure 3

• Oversupplementation with active vitamin D derivatives may suppress PTH, resulting in adynamic or low-turnover bone, possibly worsening microcracks 3

CKD-Associated Metabolic Bone Disease

• Secondary hyperparathyroidism begins when GFR falls below 60 mL/min/1.73 m² (CKD Stage 3), and levels of Vitamin D [1,25(OH)₂D₃] fall at this level of GFR 3

• The term "CKD-associated osteoporosis" acknowledges that renal osteodystrophy is a disorder of bone strength that increases fracture risk 3

• CKD-associated osteoporosis is a distinct form of osteoporosis with overlapping metabolic bone diseases, requiring tailored management strategies 3

• Bone disease in patients with CKD is complex and multifaceted, with overlapping features of renal osteodystrophy and other forms of osteoporosis (e.g., age or immobility related, postmenopausal, hypogonadal, glucocorticoid induced, or nutritional) 3

Parenteral Nutrition-Associated Metabolic Bone Disease

• MBD can be a potential complication in patients receiving chronic parenteral nutrition (PN) therapy 4

• The etiology of PN-associated MBD is multifactorial, including:

  • Underlying disease and malabsorption 5
  • Effect of medications (e.g., corticosteroids) 5
  • Toxic contaminants in the PN solution 4
  • Possible PN-related factors include aluminum contamination, increased sensitivity to vitamin D suppressing PTH secretion, and hypercalciuria induced by intravenous nutrient infusion 3

Diagnosis of Metabolic Bone Disease

• Dual-energy X-ray absorptiometry (DXA) is the gold standard for diagnosing metabolic bone disease for routine purposes 3

• Measurement of bone density cannot distinguish between osteomalacia and osteoporosis; for a more specific diagnosis, bone histology may be needed 3

• The biochemical assessment includes:

  • Serum concentrations and optionally 24-h urinary excretion of minerals 3
  • Biochemical markers of bone turnover 3
  • Plasma concentrations of PTH, 25-hydroxyvitamin D and possibly 1,25-dihydroxyvitamin D 3

• Bone biopsy remains the "gold standard" for the diagnosis of metabolic bone disease in CKD patients, using quantitative bone histomorphometry with double tetracycline labeling 3

• Bone biopsy should be considered in patients with kidney failure (Stage 5) who have:

  • Fractures with minimal or no trauma (pathological fractures) 3
  • Intact plasma PTH levels between 100 and 500 pg/mL with coexisting conditions such as unexplained hypercalcemia, severe bone pain, or unexplained increases in bone alkaline phosphatase activity 3
  • Suspected aluminum bone disease 3

Management Approaches

• Management of CKD-MBD biochemical abnormalities cannot be dissociated from the relevant clinical outcomes of bone loss and fractures 3

• For CKD patients, the calcium, magnesium, and phosphate content must aim at maintaining serum concentrations and 24-h urinary excretions within the normal range 3

• In patients on parenteral nutrition, recommended intravenous dose of vitamin D is 200 IU/day 3

• For monitoring purposes, repeated DXA measurements at yearly intervals are recommended 3

• General risk factors for developing osteoporosis should be promptly addressed, as well as factors with a possible negative impact on bone health (chronic inflammation, infections, drugs) 3

• In CKD patients, serum levels of total CO2 should be maintained at >22 mEq/L (22 mmol/L) to prevent metabolic acidosis 3