Kliniczne aspekty urazów i chorób kości 2 | Clinical Aspects of Skeletal Injuries and Diseases 2

Paget’s Disease of Bone

Paget’s disease is a chronic bone disorder characterized by the disruption of normal bone remodeling processes, resulting in enlarged, weakened, and misshapen bones.

Causes and Pathophysiology

The exact cause of Paget’s disease is unclear, though genetic and environmental factors may play a role. Some theories suggest viral infections (e.g., paramyxovirus) may trigger the disease in genetically susceptible individuals. The disease primarily affects osteoclasts, causing abnormal bone resorption and subsequent disorganized bone formation by osteoblasts, leading to structurally weak bone.

Clinical Manifestations

Paget’s disease can be asymptomatic, but when symptoms do occur, they may include:

• Bone pain: Often the first symptom, most commonly in the pelvis, spine, or legs.
• Bone deformities: Enlarged or misshapen bones, particularly in the skull, spine, and long bones.
• Fractures: The affected bones become weak and prone to fractures.
• Hearing loss: Due to involvement of the skull and compression of auditory nerves.
• Joint pain and arthritis: Especially in weight-bearing joints like hips and knees.

Diagnosis

• X-rays: Show enlarged, thickened bones with areas of increased density.
• Bone scan: Helps identify all areas of the body affected by the disease.
• Alkaline phosphatase (ALP) blood test: Elevated in patients with active disease due to increased bone turnover.

Treatment

• Bisphosphonates: First-line treatment to inhibit osteoclast activity and reduce bone turnover.
• Calcitonin: An alternative therapy for patients who cannot tolerate bisphosphonates.
• Pain management: Analgesics or anti-inflammatory drugs for bone and joint pain.
• Surgery: Required for correcting fractures, severe deformities, or joint replacement in advanced cases.

Complications

• Fractures: Weakened bones are more susceptible to breaks.
• Osteoarthritis: Paget’s can lead to joint damage due to misalignment or bone overgrowth.
• Hearing loss: Often permanent if auditory nerves are damaged.
• Heart failure: In rare cases, due to the increased blood supply required by affected bones.

Osteogenesis Imperfecta (Brittle Bone Disease)

Osteogenesis Imperfecta (OI) is a genetic disorder causing fragile bones that break easily, often from minimal trauma. It is caused by defects in the production of type I collagen, a major component of bone structure.

Types of OI

Clinical Manifestations

OI symptoms depend on the type but generally include:

• Frequent fractures: Even with minimal or no trauma.
• Bone deformities: Particularly in more severe forms (e.g., bowing of limbs).
• Blue sclera: A bluish tint to the whites of the eyes.
• Hearing loss: Occurs in adulthood due to ear bone malformations.
• Short stature: Particularly in more severe cases.
• Loose joints: Due to connective tissue abnormalities.

Diagnosis

• Genetic testing: Confirms the diagnosis by identifying mutations in collagen-related genes.
• X-rays: Show characteristic bone deformities and multiple fractures.
• Bone density testing: To assess bone strength and fragility.

Treatment

• Bisphosphonates: To increase bone density and reduce fracture risk.
• Physical therapy: Aimed at strengthening muscles and improving mobility.
• Surgical interventions: Such as rodding surgery to stabilize long bones and prevent fractures.
• Hearing aids: For patients with hearing loss.

Complications

• Recurrent fractures: Leading to chronic pain and reduced mobility.
• Scoliosis: Spinal deformities due to fragile vertebrae.
• Respiratory issues: In severe cases, due to rib fractures and deformities.

Rheumatoid Arthritis (RA)

Rheumatoid Arthritis (RA) is a chronic autoimmune disorder that primarily affects joints but can also cause significant bone destruction.

Causes and Pathophysiology

RA occurs when the immune system attacks the synovium (lining of the joints), causing inflammation and joint destruction. Over time, this leads to bone erosion and cartilage destruction.

Clinical Manifestations

The primary symptoms of RA include:

• Joint pain: Especially in the small joints of the hands and feet.
• Morning stiffness: Lasting longer than 30 minutes.
• Bone erosion: As the disease progresses, bones around affected joints deteriorate.
• Fatigue: Often accompanies other symptoms.
• Joint deformity: Advanced RA can cause significant deformities in the joints, particularly in the fingers.

Diagnosis

• Rheumatoid factor (RF) and anti-CCP antibodies: Commonly elevated in patients with RA.
• X-rays: Show joint destruction, bone erosion, and soft tissue swelling.
• MRI: Useful for detecting early bone erosion and synovitis (inflammation of the joint lining).

Treatment

• Disease-modifying antirheumatic drugs (DMARDs): Such as methotrexate, to slow disease progression.
• Biologic therapies: Target specific components of the immune system to reduce inflammation.
• Steroids: To control acute flares and reduce inflammation.
• Joint surgery: Including joint replacement, may be needed in severe cases.

Complications

• Osteoporosis: Bone loss due to chronic inflammation and steroid use.
• Joint deformities: Leading to disability and loss of function.
• Bone erosion: Irreversible damage to bones around joints.

Fibrous Dysplasia

Fibrous Dysplasia is a rare bone disorder where normal bone and marrow are replaced with fibrous tissue, leading to bone deformities, fractures, and pain.

Causes and Pathophysiology

Fibrous dysplasia is caused by a mutation in the GNAS gene, leading to abnormal fibroblast activity. The disease can affect one bone (monostotic) or multiple bones (polyostotic).

Clinical Manifestations

Symptoms of fibrous dysplasia may include:

• Bone pain: Often the first symptom.
• Bone deformities: Due to abnormal bone formation.
• Fractures: Weakened bones are prone to fractures.
• Asymmetry of facial bones: If the skull is involved.

Diagnosis

• X-rays: Show characteristic “ground glass” appearance of affected bones.
• Bone scan: To assess the extent of bone involvement.
• Biopsy: Confirms the diagnosis by demonstrating fibrous tissue in the bone.

Treatment

• Bisphosphonates: Used to reduce bone pain and prevent fractures.
• Surgical correction: For severe deformities or recurrent fractures.
• Pain management: Including NSAIDs and physical therapy.

Complications

• Fractures: Common due to bone fragility.
• Bone deformities: Particularly in the skull and long bones.
• Malignant transformation: Rarely, fibrous dysplasia can progress to osteosarcoma.

Hyperparathyroidism and Bone Disease

Hyperparathyroidism occurs when excessive parathyroid hormone (PTH) is produced, leading to increased bone resorption and weakening of the bones, a condition known as osteitis fibrosa cystica.

Causes and Pathophysiology

Primary hyperparathyroidism is usually caused by a benign tumor (adenoma) of the parathyroid glands. Secondary hyperparathyroidism occurs in response to chronic kidney disease or vitamin D deficiency.

Clinical Manifestations

Symptoms of bone involvement in hyperparathyroidism include:

• Bone pain: Due to increased bone resorption.
• Fractures: Fragile bones are prone to breaks.
• Muscle weakness: Due to the effects of elevated calcium levels.
• Kidney stones: Due to high calcium levels in the blood.

Diagnosis

• Serum calcium and PTH levels: Elevated in primary hyperparathyroidism.
• Bone X-rays: May show bone thinning or cystic bone lesions.
• DEXA scan: Measures bone density and helps assess fracture risk.

Treatment

• Parathyroidectomy: Surgical removal of the overactive gland is the definitive treatment for primary hyperparathyroidism.
• Medications: Including bisphosphonates and calcimimetics to reduce bone resorption.

Complications

• Fractures: Due to weakened bones.
• Osteoporosis: Progressive bone loss.
• Kidney stones: Leading to chronic kidney damage.

Bone Tumors (Primary and Secondary)

Bone tumors can be either primary (originating in the bone) or secondary (metastatic from another part of the body). Primary bone tumors can be benign or malignant, whereas secondary bone tumors are always metastatic.

Primary Bone Tumors

Causes and Risk Factors

The exact cause of primary bone tumors is often unknown, but several risk factors may increase the likelihood of development:

• Genetic mutations: Inherited syndromes such as Li-Fraumeni syndrome and retinoblastoma.
• Previous radiation exposure: A history of radiation therapy increases the risk of bone cancer.
• Paget’s disease of bone: In rare cases, Paget’s disease can develop into osteosarcoma.

Clinical Manifestations

• Bone pain: Often the earliest symptom, persistent and worsening over time.
• Swelling or a mass: Near the affected bone.
• Fractures: Bones weakened by the tumor may break easily.
• Systemic symptoms: Including weight loss, fever, and fatigue in more advanced cases.

Diagnosis

• X-rays: Initial imaging to detect abnormal bone growth.
• CT or MRI scans: Provide detailed images of the bone and surrounding soft tissues.
• Bone biopsy: Required for definitive diagnosis to distinguish between benign and malignant tumors.
• PET scan: Helps assess for metastasis or recurrent disease.

Treatment

• Surgical resection: The primary treatment for most bone tumors, involving the removal of the tumor with clean margins.
• Chemotherapy: Particularly important in treating osteosarcoma and Ewing sarcoma, often given before and after surgery.
• Radiation therapy: Used for tumors that are inoperable or to treat metastatic disease, especially in Ewing sarcoma and chondrosarcoma.

Complications

• Metastasis: Malignant bone tumors can spread to other parts of the body, commonly to the lungs.
• Fractures: Bone weakened by the tumor may break.
• Recurrence: Even after treatment, bone tumors may recur, requiring close monitoring.

Secondary (Metastatic) Bone Tumors

Secondary bone tumors are cancers that have spread (metastasized) to the bone from other primary sites, such as the breast, prostate, lung, or kidney.

Causes and Risk Factors

Secondary bone tumors arise when cancer cells from another part of the body travel through the bloodstream or lymphatic system and implant in the bone.

Clinical Manifestations

• Bone pain: Often severe and localized to the affected area.
• Fractures: Due to weakened bones.
• Hypercalcemia: Elevated blood calcium levels due to bone breakdown, causing confusion, nausea, and fatigue.

Diagnosis

• Bone scan: Detects areas of high metabolic activity in the bones, which may indicate metastasis.
• CT or MRI: To evaluate the extent of bone involvement.
• Biopsy: Confirms the diagnosis and identifies the primary source of cancer.

Treatment

• Palliative care: Aimed at controlling symptoms and improving quality of life.
• Radiation therapy: To relieve pain and prevent fractures.
• Surgery: In some cases, to stabilize bones weakened by metastasis.
• Systemic therapy: Includes chemotherapy, hormonal therapy (for breast and prostate cancer), and targeted therapies based on the primary cancer.

Complications

• Pathological fractures: Bones are weakened by metastatic disease and prone to fractures.
• Hypercalcemia: Can be life-threatening if not treated.
• Spinal cord compression: From tumors affecting the vertebrae, leading to paralysis or loss of function.