15.7 Musculoskeletal System Pathology: Metabolic Bone Disease, Arthropathies, and Bone Neoplasms
Key Takeaways
- Osteoporosis is the most common metabolic bone disease and produces low-trauma fractures of the vertebrae, hip, and distal forearm, diagnosed by DEXA T-score below −2.5; type I is postmenopausal (estrogen deficiency) and type II is senile.
- Osteomalacia and rickets share defective mineralization of osteoid due to vitamin D deficiency, distinguished from osteoporosis (which has normally mineralized but reduced bone); Looser zones (pseudofractures) are characteristic of osteomalacia.
- Gout produces monosodium urate crystals that are needle-shaped and negatively birefringent, classically affecting the first metatarsophalangeal joint (podagra); pseudogout contains weakly positive birefringent calcium pyrophosphate rhomboids.
- Duchenne muscular dystrophy is an X-linked recessive dystrophin deficiency with calf pseudohypertrophy, proximal weakness, markedly elevated creatine kinase, and Gowers sign, progressing to loss of ambulation by adolescence.
- Osteosarcoma occurs in the adolescent metaphysis (distal femur, proximal tibia) with osteoid production and a sunburst or Codman triangle periosteal reaction, whereas Ewing sarcoma is a small round blue cell tumor with t(11;22) and onion-skin periosteal reaction in the diaphysis.
15.7 Musculoskeletal System Pathology
The blueprint groups musculoskeletal disease into eight categories. This section covers the high-yield, frequently tested entities, emphasizing the features that separate them on a vignette.
1. Nutritional and Metabolic Bone Disease
Osteomalacia (adults) and rickets (children, open growth plates) are defective mineralization of osteoid from vitamin D deficiency; bone is soft, with Looser zones (pseudofractures) and bowing. Scurvy is vitamin C deficiency, impairing collagen hydroxylation: bleeding gums, perifollicular hemorrhage, poor wound healing, and 'woody' cork-screw hairs.
Osteoporosis is the most common metabolic bone disease: reduced bone mass with normal mineralization. Type I is postmenopausal (estrogen deficiency → trabecular loss → vertebral and distal forearm fractures); type II is senile (cortical and trabecular → hip fractures). Diagnosed by DEXA T-score < −2.5; treated with bisphosphonates, calcium/vitamin D, weight-bearing exercise, and denosumab or teriparatide in selected cases.
Osteopetrosis (marble bone disease) is the opposite—osteoclast dysfunction (e.g., carbonic anhydrase II deficiency) causing dense but brittle bone with fractures and cranial-nerve compression.
Paget disease of bone is disordered remodeling through three phases (lytic, mixed, sclerotic): markedly elevated alkaline phosphatase with normal calcium and phosphate, enlarged skull (hearing loss, hat size increase), and a small risk of osteosarcoma. Histology shows a mosaic pattern of lamellar bone with prominent cement lines.
Avascular necrosis is ischemic bone death, classically of the femoral head, after steroids, sickle cell disease, or trauma.
2. Inflammatory and Crystal Arthropathies
Osteoarthritis (OA) is degenerative, non-inflammatory, and asymmetric, with osteophytes, subchondral sclerosis, and crepitus; it affects the DIP (Heberden nodes), PIP (Bouchard), spine, knees, and hips, sparing the MCPs.
Rheumatoid arthritis is a symmetric inflammatory polyarthritis of the MCP/PIP, sparing DIP, with anti-CCP, morning stiffness, and pannus (see 15.5).
Gout is monosodium urate deposition from hyperuricemia, classically the first MTP (podagra); crystals are needle-shaped, negatively birefringent under polarized light; triggers include thiazides, alcohol, meat; tophi in chronic disease; treated with NSAIDs/colchicine acutely and allopurinol chronically. Pseudogout is calcium pyrophosphate, rhomboid, weakly positive birefringent, in the knee and wrist, often with osteoarthritis.
Ankylosing spondylitis is HLA-B27 sacroiliitis with bamboo spine on imaging, uveitis, and enthesitis. Reactive arthritis (Reiter) is also HLA-B27, post-Chlamydia/Campylobacter/Salmonella, with the triad 'can't see (uveitis), can't pee (urethritis), can't climb a tree (arthritis).' Polymyalgia rheumatica (PMR) affects those over 50 with very high ESR and proximal stiffness, and coexists with giant cell (temporal) arteritis, a vascular emergency. Dermatomyositis/polymyositis are inflammatory myopathies with proximal weakness and elevated CK; dermatomyositis has Gottron papules and heliotrope rash and carries malignancy risk. Fibromyalgia is widespread tender points with fatigue and no inflammation.
3. Congenital and Genetic Disorders
Marfan syndrome is fibrillin-1 (FBN1) defect: tall stature, arachnodactyly, lens dislocation (upward), and aortic dissection risk. Osteogenesis imperfecta is type I collagen defect: blue sclera, brittle bones, and hearing loss. Duchenne muscular dystrophy is X-linked with a frameshift dystrophin deletion: proximal weakness, calf pseudohypertrophy, Gowers sign, markedly elevated CK, progressing to loss of ambulation by age 12 and dilated cardiomyopathy. Becker is milder from in-frame deletions.
4. Musculoskeletal Neoplasms
| Tumor | Age / site | Histology / genetics | Imaging |
|---|---|---|---|
| Osteosarcoma | Adolescent, metaphysis (distal femur, proximal tibia) | Osteoid production; often p53/Rb mutation | Sunburst, Codman triangle |
| Ewing sarcoma | Adolescent, diaphysis | Small round blue cell, t(11;22) | Onion-skin periosteal reaction |
| Chondrosarcoma | Older adults, axial skeleton | Cartilage matrix | Lytic with calcified matrix |
| Osteoid osteoma | Young, proximal femur | Nidus, <2 cm | Pain relieved by NSAIDs |
| Rhabdomyosarcoma | Children, head/neck, GU | Embryonal (botryoid), alveolar | Desmin/myogenin positive |
Osteosarcoma and Ewing are the two adolescent primary bone tumors most often compared; the metaphyseal site with osteoid (osteosarcoma) versus diaphyseal small round blue cells with t(11;22) (Ewing) is the classic contrast.
5. Infections and Trauma
Osteomyelitis is most often Staphylococcus aureus; in sickle cell disease Salmonella is disproportionately common; in diabetics with foot ulcers and wet gangrene, Pseudomonas and polymicrobial flora appear. Septic arthritis is a Staph/Strep/Gonococcal emergency in a hot swollen joint. Necrotizing fasciitis (mixed anaerobes or group A strep, 'flesh-eating') spreads along fascial planes with crepitus and systemic toxicity, requiring urgent debridement. Gas gangrene is Clostridium perfringens. Traumatic injury to the musculoskeletal system completes the blueprint category.
Board signal: an adolescent with knee pain and a sunburst periosteal reaction → osteosarcoma; a young boy with calf pseudohypertrophy and Gowers sign → Duchenne; an elderly woman with hip fracture and T-score −3.0 → osteoporosis; a 60-year-old with podagra and needle-shaped negatively birefringent crystals → gout.
A 15-year-old boy presents with progressive knee pain and swelling around the distal femur. Radiography shows a destructive metaphyseal lesion with a sunburst periosteal reaction and Codman triangle. What is the most likely diagnosis and underlying lesion?
Septic arthritis is most often caused by Staphylococcus aureus overall. In a young, sexually active adult, which organism is the most common cause of septic arthritis?