Osteoporosis

PATHOGENESIS OF OSTEOPOROSIS

• Definition & Key Features
  • Osteoporosis: a structural skeletal disorder with low bone mass and bone fragility, leading to increased fracture risk.
  • Microarchitectural disruption includes perforated trabecular plates and discontinuous trabecular struts.
• Mechanisms of Low Bone Mass
  • Low peak bone mass
  • Increased bone resorption
  • Decreased bone formation
  • High-turnover osteoporosis = dominant bone resorption
  • Low-turnover osteoporosis = dominant decrease in bone formation
• Determinants of Peak Bone Mass
  • ~50% is genetically determined.
  • ~50% is environmental (e.g., physical activity, calcium intake, etc.).
• Role of Sex Hormones
  • Estrogen deficiency: major contributor in postmenopausal women.
    • Estrogen normally inhibits bone resorption.
    • Prolonged estrogen deficiency → decreased bone density (includes premenopausal estrogen-deficient states).
  • Testosterone deficiency in men → predisposes to osteoporosis; some men also need estrogen (via aromatization) for normal bone.
• Risk Factors
  • Advancing age
  • Fragility fracture history
  • Glucocorticoid therapy
  • Low body mass index
  • Family history of hip fracture
  • Smoking
  • Excess alcohol use
  • Low bone mineral density (BMD)
• Other Contributing Factors
  • Low dietary calcium/vitamin D
  • Certain medications (e.g., anticonvulsants, heparin, methotrexate)
  • Immobility/bed rest
  • Neurologic disorders → limited mobility
  • Glucocorticoid excess (most commonly iatrogenic) → inhibited osteoblast differentiation
  • Hyperparathyroidism (primary/secondary) → increased bone resorption
  • Chronic inflammatory disorders (e.g., rheumatoid arthritis, IBD), malabsorption (celiac), thyroid hormone excess, multiple myeloma, etc.
  • Anorexia nervosa → dietary deficiency + estrogen deficiency
  • Genetic disorders → osteogenesis imperfecta, homocystinuria

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OSTEOPOROSIS IN POSTMENOPAUSAL WOMEN

• Overview
  • Markedly low bone mass, often tied to estrogen deficiency and aging.
  • Clinically silent until fracture occurs (spine, hip, rib, distal radius most common).
  • Multiple vertebral fractures → thoracic kyphosis (dowager’s hump), height loss, abdominal protrusion.
• Bone Strength
  • Depends on bone mass (size, shape, microarchitecture) and bone turnover (formation vs. resorption).
• Bone Mineral Density (BMD)
  • Measured by dual energy–x-ray absorptiometry (DXA) at hip and lumbar spine.
  • Inverse relationship between BMD and fracture risk.
  • T score = SD difference from a young adult reference.
    • Normal: ≥−1.0 SD.
    • Osteopenia: between −1.0 and −2.5.
    • Osteoporosis: ≤−2.5.
  • Z score = SD difference from an age-matched reference (Z < −2.0 considered low).
• Causes of Low BMD
  • Low peak bone mass in youth/adolescence.
  • Decreased bone formation and/or increased bone resorption.
  • Excess resorption often pivotal in postmenopausal women.
• Secondary Osteoporosis Considerations
  • Conditions: vitamin D deficiency, osteomalacia, hyperthyroidism, hyperparathyroidism, celiac disease, mast cell disease, hypercortisolism, etc.
  • Initial labs: CBC, serum Ca, phosphorus, liver enzymes, creatinine, TSH, 25(OH)D.
  • Additional tests guided by clinical suspicion.
• Treatment
  1. Lifestyle: Diet, exercise, smoking cessation, limiting steroids.
     • Daily calcium 1500 mg and vitamin D 800 IU recommended.
     • Weight-bearing exercise (e.g., walking) beneficial.
  2. Pharmacologic:
     • Antiresorptive agents: estrogen, selective estrogen receptor modulators, bisphosphonates, calcitonin.
     • Anabolic agents: parathyroid hormone 1-34 (teriparatide).
     • Future potential therapies: RANKL antibodies, sclerostin inhibitors, integrin inhibitors, cathepsin K inhibitors.
  3. Monitoring:
     • Bone turnover markers at baseline, then 3–6 months.
     • DXA at 1 year, then every 2–3 years.

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OSTEOPOROSIS IN MEN

• Overview
  • Frequently underdiagnosed; often recognized after low-impact fractures or noted osteopenia on radiographs.
  • Typical fracture sites: spine, hip, ribs.
  • Multiple vertebral fractures → height loss, thoracic kyphosis, restricted pulmonary function.
• Evaluation
  • DXA at lumbar spine and hip if:
    • Low-trauma fracture, incidental osteopenia on radiograph, >4 cm height loss, or clinical risk factors.
  • T score ≤−2.5 indicates osteoporosis.
  • T score −1.0 to −2.5 indicates osteopenia.
  • Secondary Osteoporosis: consider malabsorption (celiac), hypogonadism, Cushing syndrome, chronic renal/liver disease, hypercalciuria, hyperparathyroidism, etc.
• Laboratory
  • Initial: CBC, total protein (SPEP), testosterone, Ca, phosphorus, PTH, 25(OH)D, alkaline phosphatase, liver enzymes, creatinine, TSH, 24-hour urine cortisol, calcium, creatinine.
  • Additional testing guided by results.
• Treatment
  • Lifestyle: adequate calcium/vitamin D, exercise, smoking cessation, alcohol moderation.
  • Underlying Cause: e.g., testosterone replacement if hypogonadism.
  • Pharmacologic: indicated for:
    • Men ≥50 years with vertebral/hip fracture or T score ≤−2.5.
    • Men with FRAX risk of ≥3% hip fracture or ≥20% combined osteoporotic fractures.
  • Options: primarily bisphosphonates; teriparatide (PTH 1-34) reserved for severe/refractory cases.

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CLINICAL MANIFESTATIONS OF OSTEOPOROTIC VERTEBRAL COMPRESSION FRACTURES

• Prevalence & Presentation
  • Thoracic and lumbar vertebral bodies are most commonly fractured.
  • Often at thoracolumbar junction (T11–L2).
  • May be asymptomatic and found incidentally on radiographs.
  • Acute fractures → local or radiating back pain, worsened by movement.
  • Pain typically improves over 4–8 weeks; but chronic discomfort can persist.
• Kyphosis & Height Loss
  • Multiple compression fractures → thoracic kyphosis (“dowager’s hump”) and reduced stature.
  • Neck hyperextension to maintain head position → neck discomfort.
  • Abdominal protrusion from decreased thoracic space.
  • Lowest rib may contact iliac crest → fl ank/abdominal pain.
• Fracture Patterns
  • Anterior wedge fractures
  • Biconcave (codfi sh) deformities
  • Compression fractures.
  • Grading severity by vertebral height loss:
    • Grade 1: 20–25%
    • Grade 2: 26–40%
    • Grade 3: >40%
• Evaluation & Treatment
  • Plain spine radiographs if new vertebral fracture suspected.
  • MRI if radicular symptoms or concern for other pathology.
  • BMD assessment by DXA to confirm osteoporosis.
  • Underlying cause (e.g., postmenopausal osteoporosis, steroid-induced) determines therapies.
  • Pain management with NSAIDs or analgesics.
  • Vertebroplasty/kyphoplasty for severe or persistent pain, restores vertebral height and reduces pain.

Learn more about the Treatment of osteoporosis.