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• Osteoporosis


  Characterized by progressive loss of bone mass and skeletal fragility. Patients have increased risk of fractures.

  
• Paget disease


  Disorder of bone remodeling that results in disorganized bone formation and enlarged or misshapen bones. Patients may experience bone pain, bone deformities, or fractures.

  
• Osteomalacia


  Softening of the bones most often attributed to vitamin D deficiency.

  
• Bone remodeling


  1. Osteoclasts break down bone (bone resorption)

  2. Osteoblasts synthesize new bone

  3. Crystals of calcium phosphate (hydroxyapatite) deposited in new bone matrix during mineralization

  4. Bone loss occurs when resorption exceeds formation

  
• Strategies to reduce bone loss in postmenopausal women

  • Adequate dietary intake of calcium and vitamin D
  • Weight-bearing exercise
  • Smoking cessation
  • Avoidance of excessive alcohol intake
• Calcium carbonate


  Inexpensive and commonly used calcium supplement. Contains 40% elemental calcium. Should be taken with meals.
• Calcium citrate


  Better tolerated calcium supplement. Contains 21% elemental calcium. Can be taken with or without food.
• Adverse effects of calcium supplementation include gas and bloating. Calcium may interfere with absorption of iron preparations, thyroid replacement, and fluoroquinolone and tetracycline antibiotics.
• Vitamin D


  Essential for absorption of calcium and bone health. Older patients often at risk for deficiency.
• Pharmacologic therapy for osteoporosis is warranted in

  • Postmenopausal women
  • Men aged 50 years or over who have a previous osteoporotic fracture
  • Those with a bone mineral density 2.5 standard deviations or more below that of a healthy young adult
  • Those with low bone mass (osteopenia) and high probability of future fractures

  
• Bisphosphonates


  Preferred agents for treatment of postmenopausal osteoporosis. Also used for Paget disease, bone metastases, and hypercalcemia of malignancy.

  
• Mechanism of action of bisphosphonates

  1. Bind to hydroxyapatite crystals in bone

  2. Decrease osteoclastic bone resorption

  3. Result in small increase in bone mass and decreased fracture risk

  
• Oral bisphosphonates


  Alendronate, risedronate, and ibandronate dosed daily, weekly, or monthly

  
• Absorption of oral bisphosphonates is poor (less than 1% of dose absorbed). Food and other medications significantly interfere with absorption.

  
• Bisphosphonates are rapidly cleared from plasma, primarily by binding to hydroxyapatite in bone. Elimination is predominantly via the kidney, so they should be avoided in severe renal impairment.

  
• Adverse effects of bisphosphonates

  • Diarrhea
  • Abdominal pain
  • Musculoskeletal pain
  • Esophagitis and esophageal ulcers
  • Osteonecrosis of the jaw
  • Atypical femur fractures
• Current guidelines recommend a drug holiday for some patients after 5 years of oral bisphosphonates or 3 years of zoledronic acid, due to increased risk of atypical fractures with long-term use.
• Denosumab


  Monoclonal antibody that targets receptor activator of nuclear factor kappa-B ligand, inhibiting osteoclast formation and function. Approved for treatment of postmenopausal osteoporosis in high-risk patients.
• Denosumab is considered a first-line agent for osteoporosis, particularly in patients at higher risk of fractures.
• Adverse effects of denosumab

  • Increased risk of infections
  • Dermatological reactions
  • Hypocalcemia
  • Osteonecrosis of the jaw
  • Atypical fractures

  
• Teriparatide and abaloparatide


  Recombinant parathyroid hormone and analog, respectively. Act as agonists at the parathyroid hormone receptor, stimulating osteoblastic activity and increasing bone formation and strength.
• Teriparatide and abaloparatide should be reserved for patients at high risk of fractures and those who have failed or cannot tolerate other osteoporosis therapies.
• Adverse effects of teriparatide and abaloparatide

  • Hypercalcemia
  • Orthostatic hypotension
  • Increased risk of osteosarcoma in rats
• Cumulative lifetime use of teriparatide or abaloparatide for more than 2 years is not recommended.
• Raloxifene


  Selective estrogen receptor modulator approved for prevention and treatment of osteoporosis. Has estrogen-like effects on bone and estrogen antagonist effects on breast and endometrial tissue.
• Raloxifene increases bone density without increasing the risk of endometrial cancer, and should be used as an alternative to bisphosphonates or denosumab in the treatment of postmenopausal osteoporosis.

  
• Adverse effects of raloxifene


  • Hot flashes
  • Leg cramps
  • Increased risk of venous thromboembolism
• Salmon calcitonin


  Indicated for the treatment of osteoporosis in women at least 5 years postmenopausal. Reduces bone resorption, but less effective than other agents and no longer routinely recommended.
• Adverse effects of salmon calcitonin

  • Rhinitis and other nasal symptoms