Metabolic Bone Diseases Overview

Introduction

• Lecturer: Ms Kezia Brown
• Role: Senior clinical lecturer, Consultant orthopaedic surgeon
• Topic: The ageing skeleton, specifically metabolic bone diseases.

Metabolic Bone Diseases

• Disorders of Bone Remodelling
  • Osteoporosis: resorption > formation
  • Paget's disease: increased resorption and formation
  • Osteopetrosis: decreased resorption
• Disorders of Mineralisation
  • Hyperparathyroidism
  • Vitamin D-related disorders (osteomalacia, rickets)

Osteoporosis

• Disorder of bone quantity, not quality
• Skeletal disorder with:
  • Deterioration of microarchitecture
  • Compromised bone strength
  • Increased risk of fractures

Paget's Disease of Bone

• Abnormal localised bone remodeling.
• Primarily increased osteoclast (OC) resorption.
• Increased but disorganized bone formation.
• Second most common metabolic bone disease (MBD).
• Clinical features:
  • Enlarged skull
  • Bowing of long bones
  • Large joint osteoarthritis (OA)
  • Fractures
  • Nerve compression
  • Deafness
• Polyostotic disease
• Paget's sarcoma: rare malignant change, less than 1% of Paget's cases.
  • Most commonly osteosarcoma
  • Sarcoma = malignancy from mesenchymal cells
  • Metastatic disease has poor prognosis.

Paget's Disease of Bone (cont'd)

• Pathology:
  • Abnormal osteoclasts/precursors
  • Greater in number, unusually large and hypersensitive to stimulation
  • 3 phases which can coexist in the same bone
    • Lytic: intense osteoclastic resorption
    • Sclerotic: predominant osteoblastic formation
    • Mixed: resorption and compensatory formation

Paget's Disease of Bone (cont'd)

• Investigation
  • Imaging (radiographs, bone scan)
  • Lab results (elevated ALP, marker of bone turnover)
  • Histology
• Treatment
  • OC inhibition
  • Arthroplasty

Osteopetrosis

• Defective osteoclastic resorption
• Cannot acidify Howship's lacuna
• Bone formed but not remodelled
• Dense
• Obliterated medullary canal
• Predisposition to fracture (low energy)
• Transverse fractures
• Increased risk of non/mal-union

Hyperparathyroidism

• Increase in circulating levels of PTH (parathyroid hormone).
• Primary: intrinsic abnormality of the parathyroid gland(s), pathological increase in PTH production
  • Parathyroid adenoma (85%)
• Secondary: increased PTH secretion due to hypertrophic parathyroid glands
  • Secondary to chronic hypocalcemia/hyperphosphatemia
  • Vitamin D deficiency
  • Chronic renal disease

Main effects of PTH

• Increases bone resorption
• OBs release more RANKL and less OPG
• OCs differentiate and activate
• Increased renal hydroxylation of Vitamin D (calcitriol)
• Increased RANKL release
• Increased intestinal uptake
• Increased renal uptake

Hyperparathyroidism (Symptoms and Signs)

• Bones, stones, abdominal groans, thrones and psychic moans
  • Arthritis, osteoporosis
  • Kidney stones
• Nausea, vomiting, constipation
• Fatigue, depression, confusion
• Muscle weakness, achy joints
• Increased thirst/urination

Hyperparathyroidism (Treatment)

• Primary: Parathyroidectomy (97% cure rate)
• Secondary: Treat the underlying cause (Vitamin D deficiency, chronic renal disease)

Vitamin D

• Source: sunlight or diet
• 2 hydroxylations (liver, kidneys) forming calcitriol (active form)
• Receptors throughout the body for calcium absorption
• Maintains serum phosphate
• Decreases PTH synthesis
• Increases FGF23 (feedback loop)

Rickets

• Defects in mineralisation (calcium and phosphate) prior to physeal closure.
• Reduced mineralisation at growth plates.
• Congenital (familial hypophosphatemic)
  • Inability of kidneys to absorb phosphate
• Acquired (Vitamin D deficient)
  • Lack of dietary Vitamin D or sunlight exposure resulting in decreased calcium absorption
• Orthopaedic manifestations: brittle bones, bowing of long bones, flattening of skull, enlargement of costal cartilage (cat back), dental abnormalities, irritability
• Treatment/management: Vitamin D, Calcium, Phosphate, Calcitriol, sometimes surgery

Osteomalacia

• Defects in mineralisation and reduced mineralisation at growth plates AFTER physeal closure.
• Qualitative defect of bone, unlike quantitative defect in osteoporosis.
• Causes:
  • Diet, malabsorption (coeliac), renal osteodystrophy, alcoholism, tumors
  • Drugs (Vitamin D deficiency, phosphate homeostasis disruption, altered bone mineralisation)
• Symptoms/signs include: bone and muscle pain, atypical fractures, Looser zones, femur/femoral neck fractures, proximal muscle weakness, fatigue, hip arthritis (protrusio)
• Treatment: large doses of vitamin D

Osteoporosis and Fractures (Mechanisms and Epidemiology)

• High prevalence among older women and males.
• Causes related to low energy trauma, bone density, post-menopause, secondary causes or medications.
• Bimodal distribution with peak incidence in younger males (high energy trauma)

Other Fractures/Management

• Proximal Humerus: Caused by simple falls, 3rd most common appendicular fracture, 2:1 female-to-male ratio, more complex with age. Treatment is usually a sling/traction and early rehab. Surgery for more complex cases. Patient outcomes are variable.
• Wrist Fractures: 3:1 female-to-male ratio, caused by falls. Most common MSK injury. Management includes adequate rehab but complex regional pain syndrome is quite common. Risk factor for future fracture. DEXA scan for patients > 55. (Smith's and Colles' are types)
• Pelvic fractures: Commonly caused by fall backwards, landing on buttocks. Usually involve both superior/inferior pubic rami. Treatment is often conservative.
• Hip fractures: Extremely common/increasing incidence. High morbidity/mortality. 1/3 return to function; 1/3 lose independence; 1/3 die within a year. Should be treated with surgery with MDT input.
• Atypical Femoral Fractures: Common in bisphosphonate users, and include subtrochanteric, lateral cortex, and transverse fractures of the femur. Cortical 'beaking' and inhibited osteoclast remodeling are key points. Aim to prevent complete fracture.
• Spine: Vertebral wedge compression fractures are common from falls or insufficient trauma.
  • Often affects multiple levels/Progressive deformity
  • Height loss
  • Reduced pulmonary volume
  • Distension, constipation, nausea
  • Patient may not be able to see feet or look forward.

Terminology (fractures)

• insufficient fractures: cumulative result of repeated normal loading on abnormal bone
• fragility fracture: result of forces are too weak to fracture normal bone almost always osteoporotic.

Bone Mass and Peak Bone Mass

• Bone mass decreases with age for both men and women. Men achieve peak bone mass much sooner than women.

Oestrogen and Bone

• Oestrogen has a protective effect on bone. It promotes bone formation and inhibits bone breakdown in most conditions

Explore the complexities of metabolic bone diseases, including osteoporosis, Paget's disease, and mineralisation disorders. This quiz will cover the pathophysiology, clinical features, and implications for bone health in aging individuals. Test your knowledge about the disorders of bone remodeling and mineralization.