13.2 Disorders of the Musculoskeletal System

Why musculoskeletal pathology is a scored Pathology topic

Quick Answer: Osteoporosis is too little normally mineralized bone; osteomalacia is too little mineral on a normal matrix. Put the tumor on the bone map (epiphysis, metaphysis, diaphysis) and the decade. OA is wear-and-repair of cartilage; RA is autoimmune pannus. Gout needles are yellow-parallel negative; CPPD rhombs are blue-parallel positive. Dystrophinopathies are X-linked membrane tears; inflammatory myopathies are T-cell attacks with different geography.

Metabolic and infectious bone disease

Osteoporosis is decreased bone mass with a normal mineral-to-matrix ratio. Trabeculae are thinned and perforated; cortices are thin. Fracture sites: vertebral compression (thoracic kyphosis, height loss), distal radius, femoral neck. Two classic paths:

• Postmenopausal (type I): estrogen loss unleashes osteoblast cytokines (IL-1, IL-6, TNF) and RANKL, osteoclasts accelerate, trabecular bone of vertebrae and distal radius goes first (high-turnover).
• Senile (type II): osteoblast function fades; cortical and trabecular bone both decline; hip fractures rise.

Disuse, glucocorticoids, heparin, hyperthyroidism, multiple myeloma, and malabsorption mimic or worsen the same radiograph. Labs in primary osteoporosis are typically normal calcium, phosphate, and ALP—unlike osteomalacia, primary hyperparathyroidism, and Paget disease.

Osteomalacia / rickets is undermineralized osteoid. Vitamin D deficiency, phosphate wasting, or renal osteodystrophy can do it. Children (rickets) show rachitic rosary, Harrison groove, pigeon chest, metaphyseal cupping, and bowing. Adults show Looser zones (pseudofractures) and bone pain. ALP is often high; calcium and phosphate tend to be low or low-normal. Contrast with osteoporosis: the mass may look similar on a casual film, but the chemistry and osteoid seams differ.

Osteitis fibrosa cystica of severe hyperparathyroidism is osteoclastic tunneling, peritrabecular fibrosis, and brown tumors (not neoplasms—hemorrhage and giant cells). Renal osteodystrophy mixes that picture with osteomalacia (phosphate retention, low 1,25-dihydroxyvitamin D).

Paget disease of bone (osteitis deformans) is a focal, late-adulthood disorder of chaotic osteoclast then osteoblast activity, possibly paramyxovirus-related. Three phases: lytic, mixed, sclerotic. Late bone is mosaic lamellar with cement lines. Skull enlargement, cranial-nerve compression, high-output failure through hypervascular bone, and osteosarcoma (or other sarcoma) are the feared complications. Isolated markedly elevated ALP with normal calcium and phosphate is the lab signature.

Avascular (aseptic) necrosis follows interrupted blood supply: femoral head (fracture, steroids, alcohol, sickle cell, Gaucher, caisson disease), proximal pole of scaphoid, lunate (Kienböck), talus. Dead bone keeps its architecture until creeping substitution; subchondral collapse produces a crescent sign and secondary OA.

Pyogenic osteomyelitis in children seeds the metaphysis hematogenously (Staphylococcus aureus most common). Sickle-cell disease adds Salmonella (S. aureus remains frequent). IV drug use adds Pseudomonas. Adults often have contiguous spread or vertebral osteomyelitis. Necrotic cortex is a sequestrum; the reactive periosteal sleeve is an involucrum; a subacute intraosseous abscess is a Brodie abscess. Tuberculous spondylitis (Pott disease) prefers thoracic vertebrae, destroys disc and body, and can gibbus-kyphose and drain as a cold psoas abscess.

Fracture healing is a timed repair, not a mystery: hematoma and inflammation → soft (fibrocartilaginous) callus → hard (woven bone) callus → remodeling to lamellar bone along Wolff lines. Delayed or nonunion follows motion, infection, steroids, smoking, and poor blood supply (scaphoid, femoral neck, talus).

Genetic bone diseases that still appear as one-liners: osteogenesis imperfecta (type I collagen—blue sclerae, hearing loss, fractures); osteopetrosis (failed osteoclast acidification—marble bone, marrow crowding, cranial-nerve palsies); achondroplasia (FGFR3 constitutive activity—short limbs, relatively large head, lumbar stenosis).

Bone tumors by age and site

Do not memorize every sarcoma. Put the lesion on a map of age × anatomic site × matrix.

Multiple punched-out lytic skull lesions in an older adult are myeloma until proven otherwise (organ-system blood chapter), not metastatic prostate (which is blastic).

Joint disease: OA, RA, seronegative, crystals, infection

Osteoarthritis (OA) is degeneration of articular cartilage plus attempted repair. Chondrocytes make IL-1 and TNF, matrix metalloproteinases chew proteoglycan and type II collagen, and the surface fibrillates. Subchondral bone eburnates (polished ivory), osteophytes form at margins, and subchondral cysts appear. Heberden nodes are DIP osteophytes; Bouchard nodes are PIP. Hips, knees, lumbar and cervical facets, and first CMC take the load. Morning stiffness is brief; there is no bony ankylosis and no systemic acute-phase storm. The IVD’s nucleus loses proteoglycan with age—the same matrix logic as hyaline cartilage, a useful spinal hook, but OA of the facet is synovial-joint OA, not ‘disc arthritis.’

Rheumatoid arthritis (RA) is a systemic autoimmune synovitis. HLA-DR4 (shared epitope) and citrullinated proteins drive anti-CCP antibodies (more specific than rheumatoid factor, which is IgM against IgG Fc). CD4 T cells and macrophages fill the synovium; granulation pannus erodes cartilage and bone. Joints: MCP, PIP, wrists—DIPs are typically spared (the OA/psoriatic territory). Ulnar deviation, swan-neck, and boutonniere deformities follow tendon and capsular failure. Atlantoaxial (C1–C2) ligamentous laxity can sublux and threaten the cord—the highest-yield cervical fact in this section. Extra-articular: rheumatoid nodules with fibrinoid necrosis, interstitial lung disease, Felty syndrome (RA, splenomegaly, neutropenia), anemia of chronic disease, Baker cysts. Morning stiffness is prolonged. Ankylosis can occur after cartilage is gone.

Seronegative spondyloarthropathies share HLA-B27 (MHC class I), axial joints, enthesitis, and absence of rheumatoid factor.

Gout is monosodium urate in tissues. Most adults are underexcretors; overproduction includes HGPRT deficiency (Lesch-Nyhan: X-linked, self-mutilation, dystonia) and high cell turnover. Acute attack: first MTP (podagra), night, neutrophils. Negatively birefringent needle crystals are yellow when parallel to the slow ray of the compensator. Tophi are granulomas around urate in helix, olecranon, and Achilles. Precipitants: alcohol, thiazides, meat, trauma. Do not tap through cellulitis; do not call calcium pyrophosphate gout.

Calcium pyrophosphate deposition (CPPD, pseudogout) is rhomboid, positively birefringent (blue when parallel) crystals, classically the knee, with chondrocalcinosis on film. Associations: aging, hemochromatosis, hyperparathyroidism, ochronosis. Hydroxyapatite Milwaukee shoulder is a different basic-calcium-phosphate disease of elderly women.

Infectious arthritis is a closed-space emergency: hot monoarticular joint, S. aureus most common overall; Neisseria gonorrhoeae in sexually active adults (migratory polyarthralgia, tenosynovitis, then knee or wrist). Lyme (Borrelia burgdorferi) produces a late large-knee effusion. Sickle cell adds Salmonella into bone more than joint, but S. aureus still matters.

Muscle: dystrophy, inflammation, denervation

Duchenne muscular dystrophy is X-linked out-of-frame mutation of DMD at Xp21: dystrophin is absent, the sarcolemma tears with contraction, creatine kinase is very high, and muscle is replaced by fat and fibrosis (calf pseudohypertrophy). Boys present with waddling gait and Gowers sign (using hands to climb the legs). Death is respiratory or cardiomyopathy. Becker is in-frame: some internally truncated dystrophin, later onset, still cardiac risk. Female carriers can have mild CK elevation and cardiomyopathy.

Myotonic dystrophy type 1 is autosomal-dominant CTG expansion in DMPK (anticipation via maternal transmission): distal weakness, grip myotonia, cataracts, arrhythmia, testicular atrophy, frontal balding.

Denervation (root, plexus, or motor neuron) produces angular atrophic fibers, then fiber-type grouping after reinnervation by sprouting. Fasciculations are a clinical LMN sign. Contrast with disuse atrophy (type-II fiber smallness without grouping) and with the dystrophic pattern (rounded hypertrophic fibers, necrosis, regeneration, fibrosis). Myasthenia gravis is NMJ antibody disease (immune chapter) and shows no dystrophic biopsy.

A herniated lumbar disc that chemically inflames a traversing root is radiculopathy—denervation if axons die—not a primary myopathy. Keep the lesion on the correct side of the neuromuscular map when a stem gives CK, biopsy, or a Gowers sign.