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

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.

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.

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.