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Updated: May 3 2023

Osteopenia & Osteoporosis

4.4

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(104)

Images
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https://upload.orthobullets.com/topic/9032/images/osteoporotic_bone.jpg
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https://upload.orthobullets.com/topic/9032/images/dexa graph 2.jpg
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  • Summary
    • Osteopenia & Osteoporosis represent a continuum of conditions that present with a decrease in bone mass and disrupted bone microarchitecture most commonly as a result of increased age, menopause, and metabolic abnormalities.
    • Diagnosis is made with a lumbar-based DEXA scan with osteopenia having a T-score of 1 to 2.5 standard deviations below the peak bone mass of a 25-year-old individual, and osteoporosis having a T-score >2.5 standard of deviations below the peak bone mass of a 25-year-old individual.
    • Treatment involves a multidisciplinary approach with medical management and physical activity to increase bone mineral density and to help prevent fractures.
  • Epidemiology
    • Incidence
      • 10 million Americans and 200 million people worldwide have osteoporosis
      • 34 million Americans have osteopenia
      • 1.5 million osteoporotic fractures occur each year
        • 700,000 are vertebral fractures
        • 300,000 are hip fractures
        • 200,000 are wrist fractures
    • Demographics
      • male: female ratio is 1:4
        • men have a higher prevalence of secondary osteoporosis (60%) including
          • hypogonadism
          • glucocorticoid excess
          • alcoholism
      • age bracket
        • osteoporosis
          • postmenopausal osteoporosis is highest in women aged 50-70 years
          • senile osteoporosis begins after 70 years
          • secondary osteoporosis begins at any age
        • fractures
          • wrist fractures occur most commonly at age 50-60 years
          • vertebral fractures occur most commonly at age 60-70 years
          • hip fractures occur most commonly at age 70-80 years
    • Anatomic location
      • vertebral body > peritrochanter femur > distal radius
    • Risk factors
      • table of risk factors
  • Etiology
    • Pathophysiology
      • quantitative, not qualitative, disorder of bone mineralization
      • factors
        • failure to build peak bone mass as a young adult
        • bone loss in later life
    • Genetics
      • Polymorphisms in the genes for the calcitonin receptor, estrogen receptor-1, type I collagen alpha-1 chain, or the vitamin D receptor have been shown to be associated with osteoporosis
    • Associated conditions
      • fragility fractures
        • direct relationship between degree of bone loss and fractures
        • kyphotic deformity can arise from vertebral body fractures
        • pelvic ring insufficiency fractures most often treated with bed rest and analgesia
        • total hip arthroplasty with constrained components are a risk factor for fragility fractures
    • Associated with 20% increase in mortality
      • men have higher mortality rates following hip fractures than women
    • Associated with increased morbidity
      • reduced quality of life
      • only one-third of patients with hip fractures return to their previous level of function
    • History of 1 hip fracture results in up to 10 fold increased risk of 2nd hip fracture
  • Classification
      • Type I vs. Type II Osteoporosis
      • Type I
      • (Post menopausal)
      • Type II
      • (Senile)
      • Age group
      • Postmenopausal (highest incidence in 50-70 years old)
      • >70 years old
      • Bone affected
      • Almost exclusively trabecular
      • Trabecular > cortical
      • Bones fractured
      • Distal radius and vertebral
      • Hip and pelvis
      • Effect on calcium
      • Net negative change in calcium levels because of decreased intestinal absorption and increased urinary excretion of calcium.
      • Poor calcium absorption
      • Effect on Vit D
      • Reduced circulating levels of total (but not free) 1,25 dihydroxyvitamin D.
  • Imaging
    • Radiographs
      • indications
        • suspicion of fracture
        • loss of height
        • pain in thoracic or lumbar spine
      • recommended views
        • lateral spine radiograph
        • AP pelvis or hip
      • findings
        • thinned cortices
        • loss of trabecular bone
        • kyphosis
        • codfish vertebra
      • sensitivity and specificity
        • usually not helpful unless > 30% bone loss
    • DEXA Scan (Dual Energy Xray Absorptiometry)
      • usually performed in
        • lumbar spine: measures BMD from L2 to L4 and compiles scores
        • hip: measure BMD from femoral neck, trochanter, and intertrochanter region and compiles scores
      • sensitivity and specificity
        • most accurate with the least radiation exposure
      • DEXA Scan definitions
      • BMD
      • Absolute, patient-specific score determined from certain anatomic areas
      • T-Score
      • BMD relative to normal young matched controls (30-year-old women)
      • Z-Score
      • BMD relative to similar-aged patients
      • L2-4 lumbar density of 1 to 2.5 standard of deviations (T score -1 to -2.5) below the peak bone mass of a 25-year-old individual
      • Osteoporosis
      • L2-4 lumbar density > 2.5 standard of deviations (T score <-2.5) below the peak bone mass of a 25-year-old individual
  • Studies
    • Labs
      • 25 hydroxyvitamin D level
        • low 25 hydroxy cholecalciferol levels (25 hydroxy vit D) in patients sustaining low energy fractures
      • Other labs may be drawn to rule out other causes of osteoporosis (endocrine, hematologic, malignancy, etc)
        • labs are generally normal in osteoporosis
    • Biopsy
      • after tetracycline labeling
      • indications
        • may be helpful to rule out osteomalacia
    • Histology
      • thinned trabeculae
      • decreased osteon size
      • enlarged Haversian and marrow spaces
      • osteoclast ruffled border
        • Increases osteoclast ruffled border seen with
          • PTH
          • 1,25 dihydroxy Vit D3
          • Prostaglandin E
        • flattened ruffled border seen with
          • Bisphosphonates
          • Calcitonin
  • Differential
      • Osteoporosis vs. Osteomalacia 
      • Osteroporosis
      • Osteomalacia
      • Defintion
      • Reduced bone mass, normal mineralization
      • Bone mass variable, reduced mineralization
      • Age
      • Postmenopausal (Type I) or elderly (Type II)
      • Any age
      • Etiology
      • Endocrine abnormality, age, idiopathic, inactivity, alcohol, calcium deficiency
      • Vit D deficiency or abnormal vit D pathway, hypophosphatemia, hypophosphatasia, renal tubular acidosis
      • Symptoms and signs
      • Pain and tenderness at fracture site
      • Generalized bone pain and tenderness
      • Xray
      • Axial fracture predominance
      • Appendicular fracture predominance, symmetric, includes pseudofractures (Looser zones)
      • Serum Ca
      • Normal
      • Low or normal
      • Serum PO4
      • Normal
      • Low or normal
      • ALP
      • Normal
      • Elevated (except hypophosphatasia)
      • Urinary Ca
      • High or normal
      • Normal or low (high in hypophosphatasia)
      • Bone biopsy
      • Tetracycline labeling normal
      • Tetracycline labeling abnormal
  • Treatment
    • Nonoperative
      • lifestyle modification & vitamins
        • indications
          • calcium and Vitamin D
      • pharmacologic treatment
        • indications
          • 2008 National Osteoporosis Foundation Guidelines for Pharmacologic Treatment of Osteoporosis suggests that pharmacologic treatment be considered for
          • postmenopausal women and men >= 50yrs old with:
            • hip/vertebral fracture
            • T score between -1.0 and -2.5 at the femoral neck/spine and
              • 10-year risk of hip fracture ≥ 3% or
              • 10-year risk of major osteoporosis-related fracture ≥ 20% by FRAX calculation
            • T score -2.5 or less at the femoral neck/spine.
        • pharmacologic agents
          • calcium and Vitamin D
          • bisphosphonates
          • Conjugated Estrogen-progestin hormone replacement (HRT)
          • Estrogen-only replacement (ERT)
          • Salmon calcitonin (Fortical or Miacalcin)
          • Raloxifene (Evista)
          • Teriparatide (Forteo)
    • Operative
      • osteoporotic vertebral compression fracture
      • femoral neck fracture
      • distal radius fracture
  • 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
    • Osteonecrosis of the jaw (ONJ) is associated with IV bisphosphonates (but not oral bisphosphonates)
      • incidence
        • rare
      • treatment
        • stop inciting medication such as a bisphosphonate or Denosumab
    • Atypical subtrochanteric transverse stress fractures (in patients on long-term bisphosphonates)
      • incidence
        • rare
      • mechanism
        • extremely low bone turnover rates
        • shown by reduced markers of bone resorption (e.g. urinary collagen type 1 cross-linked N-telopeptide, NTx)
      • treatment
        • operative fixation with an intramedullary nail and stop bisphosphonates
          • Drug holidays are contraindicated in patients with worsening BMD or on chronic corticosteroids 
  • Prognosis
    • Prior fragility fracture is the strongest predictor of a future fracture from low energy trauma
    • Vertebral fractures
      • associated with 15% increase in 5-year mortality
      • associated with increased morbidity
        • back pain
        • loss of height
        • poor balance
        • respiratory compromise
          • restrictive lung disease
          • pneumonia
      • history of 1 vertebral fracture results in 5 fold increased risk of 2nd vertebral fracture and 5 fold increased risk of hip fracture
      • history of 2 vertebral fractures is the strongest indicated for further compression fractures in postmenopausal women
    • Hip fractures
      • associated with 20% increase in mortality
        • men have higher mortality rates following hip fractures than women
      • associated with increased morbidity
        • reduced quality of life
        • only one-third of patients with hip fractures return to their previous level of function
      • history of 1 hip fracture results in up to 10 fold increased risk of 2nd hip fracture
    • FRAX score
      • WHO fracture risk assessment tool that calculates the 10-year risk of hip fracture and 10-year risk of major osteoporosis-related fractures
      • factors include age, sex, personal history of fracture, low BMI, oral steroid use, secondary osteoporosis, parental history of hip fracture, smoking status and alcohol intake
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