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Updated: Mar 28 2025

Osteopenia & Osteoporosis

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  • Summary
  • Epidemiology
  • Etiology
  • Classification
  • Imaging
  • Studies
  • Differential
  • Treatment
  • Pharmacologic Agents
    • Bisphosphonates
      • 1st line therapy
      • indications for pharmacologic treatment
        • hip or vertebral fracture
        • T-score <2.5 at the femoral neck or spine (after exclusion of secondary causes)
        • low bone mass (T-score between -1.0 and -2.5) and
          • 10-year probability of a hip fracture ≥ 3% or greater or
          • 10-year probability of a major osteoporosis-related fracture ≥ 20% based on WHO algorithm/FRAX
      • mechanism
        • accumulate at sites of bone remodeling and are incorporated into bone matrix
        • are released into acid environment once bone is resorbed, and are then taken up by osteoclasts
        • decrease osteoclastic bone resorption, flattening of osteoclast ruffled border and increased osteoclast apoptosis
        • renal excretion without undergoing metabolism
        • exact mechanism depends on presence of nitrogen on alkyl chain (see table below)
      • technique
        • improved rates of treatment when coordinated by treating orthopedic surgeon and referral to osteoporosis clinic is made
        • DEXA scan and referral to endocrinologist
      • outcomes
        • alendronate reduces the rate of hip, spine, and wrist fractures by 50%
        • risedronate reduces vertebral and nonvertebral fractures by 40% (each) over 3 years
        • IV zoledronic acid reduces the rate of spine fractures by 70% and hip fractures by 40% over 3 years
      • Osteoporosis medications
      • Drug
      • Indications
      • Mechanism
      • Effects
      • Characteristics
      • Contraindications/
      • Adverse Effects
      • Prophylactic in all patients, best for Type II (senile)
      • Calcium reduces fracture risk by 34%.
      • Vit D supplementation reduces hip fracture risk by 10% and nonvertebral fracture risk by 7%.
      • High dose vitamin D (median, 800IU/d) reduces hip fractures by 24% and nonvertebral fractures by 30%
      • Daily calcium requirements are as follows:
      • -Age 1-3yrs - 500mg/d
      • -Age 4-8yrs - 800mg/d
      • -Age 9-18yrs - 1000 to 1500mg/d
      • -Age >50 yrs- 1200 to 1500 mg/d
      • Vitamin D requirement is 800-1,000 IUs
      • Non-nitrogen-containing bisphosphonates
      • T score <-2.5SD, fragility fracture of the hip, in both men and women
      • Produce toxic ATP analog
      • Etidronate, Clodronate, Tiludronate
      • Esophagitis, dysphagia, gastric ulcers, osteonecrosis of the jaw (ONJ), atypical subtrochanteric fractures
      • Nitrogen-containing bisphosphonates
      • T score <-2.5SD, fragility fracture of the hip, in both men and women
      • Inhibit farnesyl pyrophosphate synthase (mevalonate pathway)
      • Alendronate reduces vertebral fractures by 48% and nonvertebral fractures by 47%.
      • Risedronate reduces vertebral fractures by 65% and nonvertebral fractures by 39%.
      • Ibrandronate reduces vetebral fracture risk by 77%, hip fractures by 41%, and nonvertebral fractures by 15%.
      • Pamidronate, Alendronate (Fosamax), Risedronate (Actonel), Zolendronate (Reclast), Ibandronate (Boniva)
      • Esophagitis, dysphagia, gastric ulcers, ONJ, atypical subtrochanteric fractures
      • Conjugated Estrogen-progestin hormone replacement
      • In women with Type I (within 6 years of menopause)
      • Decreases the risk of hip fracture, but it also led to small increases in a woman's risk of breast cancer, CAD and heart attack, stroke, PE, DVT, and Alzheimer's disease
      • Estrogen-only replacement
      • Indicated for women with prior hysterectomy
      • Estrogen receptors are present on osteoblasts and osteoclasts
      • Taking unconjugated estrogen (alone) increases the risk of endometrial hyperplasia / uterine cancer)
      • Testosterone
      • Men with low levels of testosterone
      • Not yet approved by FDA for osteoporosis
      • Salmon calcitonin
      • (Fortical or Miacalcin)
      • Women >5y postmenopause, decreases pain in acute vertebral compression fractures (acts as a neurotransmitter)
      • Binds membrane receptors on osteoclasts to inhibit resorption
      • Injection or nasal spray (destroyed by gastric acid)
      • Intranasal - Transient rhinitis.
      • Injectable - nausea, vomiting, flushing, hypersensitivity reactions
      • Raloxifene (Evista)
      • Women
      • Agonist on estrogen receptors in bone (reduce osteoclast resorption).
      • Antagonizes estrogen receptor in breast, reducing breast cancer risk.
      • Selective estrogen receptor modulator (SERM), slows bone resorption, and mild increase in bone thickness.
      • Reduces risk of vertebral fractures only (not non-vertebral fractures)
      • Hot flashes, leg cramps.
      • Contraindicated in patients with VTE
      • Severe osteoporosis/high fracture risk
      • Receptors on osteoblasts (activates osteoblasts) and renal tubule cells, also stimulates intestinal absorption Ca and PO4
      • 1-34 amino-terminal residues of parathyroid hormone (1-84) ;given by daily subcutaneous injections (continuous infusion leads to bone resorption)
      •  Transient hypercalcemia, dizziness, nausea, headache.
      •  Contraindicated in Paget's disease due to potential osteosarcoma risk
      • Postmenopausal women at high risk of fracture
      • Monoclonal Ig2 against RANKL (inhibits binding of RANKL to RANK, like osteoprotegerin)
      • Reduced vertebral fractures by 68%, hip fractures by 40%, nonvertebral fractures by 20%.
      • SC injection to arm, thigh, abdomen
      •  Arthralgia, nasopharyngitis, back pain, osteonecrosis of the jaw
      •  Contraindicated in severe hypocalcemia
      • Postmenopausal women with history of osteoporotic fracture, multiple risk factors for fracture, or who have failed or are intolerant to other osteoporosis therapy
      • Humanized monoclonal Ig2 that activates Wnt pathway by binding sclerostin (sclerostin normally inhibits Wnt pathway).
      • Promotes bone formation and inhibits resorption.
      • Reduced new vertebral fracture by 73% through month 12 and by 75% through month 24
      • SC monthly injections
      • Hyperostosis, cardiovascular events, osteoarthritis, and cancer, osteonecrosis of the jaw, atypical femoral fracture
  • Complications
  • Prognosis
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