Harvey's Garden

Osteoporosis

Properties2
tagst1
aliases—

4 min read

Bone resorption by osteoclasts outpaces bone formation by osteoblasts.

Etiology

  • Demographics: Postmenopausal females (most common), advanced age (screening ≥65 yo), White/Asian ethnicity.
  • Modifiable Risk Factors:
    • Low body weight (BMI < 127 lbs / 58 kg).
      • Not obesity c
    • Sedentary lifestyle / prolonged immobilization.
    • Tobacco use, excessive EtOH (≥3 drinks/day).
    • Inadequate dietary Calcium and Vitamin D.
  • Secondary / Non-modifiable Causes:
    • Medications: Chronic systemic glucocorticoids (≥5 mg/day prednisone equivalent for ≥3 mos), anticonvulsants (Phenytoin, Carbamazepine), PPIs, Heparin, Aromatase inhibitors, GnRH agonists.
    • Endocrine: Hyperthyroidism, primary hyperparathyroidism, Cushing syndrome, hypogonadism / premature ovarian failure (<40 yo).
    • Gastrointestinal: Celiac disease, IBD, status-post bariatric (Roux-en-Y) surgery, malabsorption. c
    • Other: Multiple myeloma, RA, CKD, anorexia nervosa.
MedicationPossible Mechanism
Anticonvulsants that induce cytochrome P450 (phenobarbital, phenytoin, carbamazepine)↑ Vitamin D catabolism
Aromatase inhibitors↓ Estrogen
Medroxyprogesterone↓ Testosterone & estrogen
GnRH agonists (long term)↓ Testosterone & estrogen
Proton pump inhibitors↓ Calcium absorption
Glucocorticoids, Unfractionated heparin↓ Bone formation

Pathophysiology

Clinical features

Diagnostics

  • Screening (USPSTF):
    • All females ≥65 yo via DEXA scan. c
    • Postmenopausal females <65 yo with risk factors (10-year fracture risk equivalent to a 65-yo White female [FRAX score ≥8.4%] or chronic steroid use).
  • Confirmatory / Gold Standard: DEXA scan (Dual-energy X-ray absorptiometry) of lumbar spine and femoral neck/total hip.
    • T-score ≤ -2.5: Osteoporosis.
    • T-score -1.0 to -2.5: Osteopenia.
    • T-score > -1.0: Normal.
    • Note: Z-score ≤ -2.0 (compared to age-matched controls) indicates secondary causes in premenopausal women, men <50 yo, and children.
  • Clinical Diagnosis of Osteoporosis (Treat regardless of DEXA):
    • Fragility fracture of hip or vertebra (regardless of T-score).
    • Osteopenia (T-score -1.0 to -2.5) + high FRAX score (10-yr major fracture risk ≥20% or 10-yr hip fracture risk ≥3%).
  • Key Labs:
    • Serum Ca, PO4, ALP, and PTH are typically NORMAL in primary osteoporosis.
    • Secondary workup (if suspected or Z-score ≤ -2.0): 25-OH Vitamin D, TSH, Cr/eGFR, SPEP/UPEP, 24-hr urine Calcium.
  • Imaging:
    • Plain Radiographs: Low sensitivity for bone loss (detectable only after >30–50% demineralization); indicated to evaluate acute back pain for vertebral height loss / wedge deformity.

Treatment

  • Non-Pharmacological (All patients):
    • Weight-bearing exercise, smoking cessation, limit alcohol.
    • Calcium (1200 mg daily) and Vitamin D3 (800–1000 IU daily) supplementation. c
    • Fall prevention strategies.
  • Pharmacological Indications:
    • DEXA T-score -2.5.
    • History of hip or vertebral fragility fracture.
    • Osteopenia (T-score -1.0 to -2.5) with FRAX 10-year probability of major osteoporotic fracture 20% or hip fracture 3%.
  • First-Line Therapy: Oral Bisphosphonates (Alendronate, Risedronate). c
    • Mechanism: Inhibit osteoclasts to decrease bone resorption.
    • Administration: Must take on an empty stomach with a full glass of water and remain upright for 30 minutes to prevent pill-induced esophagitis.
    • Contraindications: GERD, esophageal stricture, achalasia, CKD (GFR < 30-35 mL/min).
    • Key Side Effects: Atypical femur fractures, osteonecrosis of the jaw (ONJ) (rare, linked to long-term use or dental procedures).
  • Alternative Therapies:
    • IV Bisphosphonates (Zoledronic acid): Used if oral form is contraindicated, not tolerated, or patient has poor compliance.
    • SERMs (Raloxifene): Agonist at bone, antagonist at breast/uterus. Used in postmenopausal women with high breast cancer risk. Note: Increases risk of DVT/PE; worsens hot flashes.
    • Denosumab (RANKL inhibitor): Subcutaneous injection every 6 months. Safe in patients with CKD.
    • Teriparatide (Recombinant PTH): Anabolic agent (stimulates osteoblasts). Reserved for severe osteoporosis (T-score < -3.5 or multiple fractures). Note: Max use 2 years due to potential risk of osteosarcoma.
  • Teriparatide, Abaloparatide
  • Recombinant human parathyroid hormone that increases osteoblastic activity → increased bone growth
    • Pulsatile PTH secretion has an anabolic effect on bone metabolism, stimulating osteoblast proliferation, decreasing osteoblast apoptosis, and inducing increased formation of new bone.  Recombinant PTH analogues (eg, teriparatide) are used to treat severe osteoporosis; these analogues promote bone remodeling by inducing increased resorption of old bone while stimulating a corresponding increase in new bone production, resulting in a net increase in total bone mass (ie, positive bone balance).
    • Also increases gastrointestinal calcium absorption & renal tubular calcium reabsorption

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