OSTEOPOROSIS REVIEW MEDICATIONS FOR OSTEOPOROSIS









Risk factors for osteoporosis included in the FRAX tool
Risk factor Comment
Age
  • Age-related bone loss occurs after age 60 in women and men
  • Occurs at a rate of 0.5% per year
Female
(Menopause)
  • There is accelerated bone loss during the menopause transition
  • Bone loss up to 10% may occur in some women
Low BMI (< 20)
  • See BMI for more
Previous fracture
  • A previous fracture in adult life occurring spontaneously, or a fracture arising from trauma which, in a healthy individual, would not have resulted in a fracture
Parental hip fracture
  • History of a hip fracture in mother or father
Oral corticosteroids
  • If ever received ≥ 5 mg/day of prednisone or equivalent for > 3 months
Current smoking
Alcohol intake
  • ≥ 3 drinks a day
Rheumatoid arthritis
Chronic diseases
(secondary osteoporosis)
  • Osteogenesis imperfecta
  • Hyperthyroidism (if untreated and long-standing)
  • Hypogonadism and premature menopause (< 45 years)
  • Chronic malnutrition and malabsorption (e.g. celiac, short bowel syndrome)
  • Chronic liver disease







USPSTF osteoporosis screening recommendations
Screen the following with DXA scanning:

  • Women
    • ≥ 65 years: screen all women
    • 50 - 64 years: screen women whose 10-year risk of fracture is ≥ 9.3% (based on the FRAX tool)

  • Men - evidence insufficient to recommend screening
Endocrine Society osteoporosis screening recommendations in men
Screen the following with DXA scanning:

  • Men
    • ≥ 70 years: screen all men
    • 50 - 69 years: screen if any of the following risk factors are present:
      • History of fracture after age 50
      • Delayed puberty
      • Hypogonadism
      • Hyperparathyroidism
      • Hyperthyroidism
      • COPD
      • Corticosteroid use
      • GnRH agonists use
      • Alcohol abuse or smoking
      • Other causes of secondary osteoporosis (ex. rheumatoid arthritis)


Estimated time interval for at least 10% of women in each
group to transition to osteoporosis on BMD testing
Initial BMD Interval (95% CI)
Normal
T-score (-1.0 or higher)
16.8 years (11.5–24.6)
Mild osteopenia
T-score (-1.01 to -1.49)
17.3 years (13.9 – 21.5)
Moderate osteopenia
T-score (-1.50 to -1.99)
4.7 years (4.2 – 5.2)
Advanced osteopenia
T-score (-2.0 to -2.49)
1.1 years (1.0 – 1.3)




Classification criteria for BMD T-scores
Category T-score
Normal -1 or above
Osteopenia -1.0 to -2.5
Osteoporosis -2.5 or below

Classification criteria for Z-scores
Category Z-score
Within expected range greater than -2.0
Below expected range for age -2.0 and below





Medical conditions associated with osteoporosis
Condition Comment
Hyperparathyroidism
  • May be primary or secondary
  • Marked by elevated calcium and PTH levels
Cushing's syndrome
Gastrointestinal disorders
  • Celiac disease, inflammatory bowel disease, gastric bypass, etc.
  • Decreased calcium and vitamin D absorption
Hyperthyroidism
  • Check TSH
End-stage kidney disease
  • Decreased phosphate excretion and decreased vitamin D conversion
    by the kidneys leads to hypocalcemia and elevated PTH levels
Hyperprolactinemia
  • Causes hypogonadal state that leads to bone loss
Hemochromatosis
  • Iron deposition in pituitary cells leads to secondary hypogonadism
  • Check ferritin level
Athletic amenorrhea
  • Marked by excessive exercise, low calorie intake, menstrual dysfunction,
    and low bone mass
Monoclonal gammopathies
  • Marked by osteolytic bone lesions and hypercalcemia
  • Check serum and urine protein electrophoresis/immunofixation


Medications associated with osteoporosis
Medication Comment
Anticonvulsants
  • Specifically carbamazepine, phenobarbital, phenytoin, and primidone
  • Drugs decrease levels of vitamin D through enzyme induction
Aromatase inhibitors
  • Block estrogen synthesis
  • Used to treat and prevent breast cancer
  • Drugs include Anastrozole (Arimidex®) and Exemestane (Aromasin®)
Depo Provera®
  • Popular birth control method
  • Suppresses estrogen levels
Glucocorticoids
Lithium
  • Lithium may raise parathyroid levels leading to bone mineral loss
SGLT2 inhibitors
  • Medications include Invokana®, canagliflozin, Farxiga® etc.
  • SGLT2 inhibitors, particularly canagliflozin, have been shown to
    decrease BMD and increase fracture risk
Proton pump inhibitors
  • Medications include Prevacid®, Nexium®, Prilosec®, etc.
  • In observational studies, long-term (> 1 year) PPI use
    has been associated with an increased risk of fracture
  • Calcium absorption is affected by acid-reducing agents
Glitazones
  • Actos® and Avandia®
  • Glitazones have been associated with an increased risk of fractures
  • See glitazones and fractures for more
Thyroid hormone replacement
  • Excessive thyroid hormone replacement can cause osteoporosis
  • See hypothyroidism for more
Immunomodulators
  • Methotrexate, cyclosporine, tacrolimus, etc.
GnRH agonists
  • Leuprolide (Lupron®), Goserelin (Zoladex®), etc.
  • Used to treat prostate cancer and endometriosis
  • GnRH agonists overstimulate the pituitary and cause it to
    stop releasing FSH and LH. This causes a hypogonadal state.


  • **High risk is not clearly defined. In general, patients who meet the criteria for initiating therapy are considered high risk.
  • A - International Osteoporosis Foundation recommendation
  • B - Amer Assoc of Clinical Endocrinologists recommendation
  • C - Endocrine Society recommendation
  • Reference [1,2,4]
Osteoporosis treatment recommendations
for postmenopausal women and men age 50 years and older
Pharmacological treatment is recommended in women and men with any of the following:

  • History of hip or spine fracture (clinical or subclinical)
  • T-score of -2.5 or less at the spine, femoral neck, or total hip
  • T-score between -1.0 and -2.5 with a 10-year risk of ≥ 3% for a hip fracture
    or ≥ 20% for major osteoporosis-related fracture based on the FRAX tool [A,B,C]

Choice of therapy in postmenopausal women
  • First line:
    • Alendronate (Fosamax®)
    • Risedronate (Actonel®)
    • Zoledronic acid (Reclast®)
    • Denosumab (Prolia®)
  • Second line:
    • Ibandronate
    • Raloxifene (Evista®)
  • Third line:
    • Calcitonin (Miacalcin®)
  • Other
    • Consider teriparatide (Forteo®) in patients at very high risk of fracture and in those who
      failed bisphosphonate therapy
    • Combination therapy is not recommended [B]
Choice of therapy in men
  • First line:
    • Alendronate (Fosamax®)
    • Risedronate (Actonel®)
    • Zoledronic acid (Reclast®)
    • Teriparatide (Forteo®)
    • Denosumab (Prolia®) - in men receiving androgen-deprivation therapy
  • Men with recent hip fracture:
    • Zoledronic acid (Reclast®) [C]
Monitoring therapy
  • BMD testing with DXA scan every 2 years is recommended [A]
Stopping therapy
  • No pharmacologic therapy should be considered indefinite in duration
  • Bisphosphonates may have residual effects even after treatment discontinuation
  • After 3 - 5 years of therapy with bisphosphonates, reassess fracture risk
    with history, DXA scanning, and vertebral imaging if indicated
  • It is reasonable to discontinue bisphosphonates after 3 to 5 years
    in patients who appear to be at modest risk of fracture
  • In patients who are at high risk**, therapy should be continued [A]


  • Reference [7]
ACR recommendations for postmenopausal women and men > 50 years old
STEP 1 - Assess fracture risk category

  • Low risk
    • FRAX calculated 10-year risk of major osteoporotic fracture ≤ 10%
  • Medium risk
    • FRAX calculated 10-year risk of major osteoporotic fracture 10 - 20%
  • High risk (any of the following)
    • FRAX calculated 10-year risk of major osteoporotic fracture > 20%
    • T-score ≤ -2.5
    • History of fragility fracture
Recommended treatment

  • Low risk
    • Glucocorticoids < 7.5 mg/day for ≥ 3 months - none recommended
    • Glucocorticoids ≥ 7.5 mg/day for ≥ 3 months - alendronate, risedronate, or zoledronic acid
  • Medium risk
    • Glucocorticoids < 7.5 mg/day for ≥ 3 months - alendronate or risedronate
    • Glucocorticoids ≥ 7.5 mg/day for ≥ 3 months - alendronate, risedronate, or zoledronic acid
  • High risk
    • Glucocorticoids < 5 mg/day for ≤ 1 month - alendronate, risedronate, or zoledronic acid
    • Glucocorticoids ≥ 5 mg/day for ≤ 1 month or any dose used for > 1 month - alendronate,
      risedronate, zoledronic acid, or teriparatide

  • Reference [7]
ACR recommendations for premenopausal women and men < 50 years old
  • Patient with no fragility fracture - inadequate data for recommendation
  • Patient with a fragility fracture - see below for treatment recommendations
Recommended treatment for patients with fragility fracture

  • Women (nonchildbearing potential) or men < 50 years old
    • Glucocorticoids for 1 - 3 months
      • Prednisone ≥ 5 mg/day: alendronate or risedronate
      • Prednisone ≥ 7.5 mg/day: zoledronic acid
    • Glucocorticoids for > 3 months - alendronate, risedronate, zoledronic acid, or teriparatide

  • Women (childbearing potential)
    • Glucocorticoids for 1 - 3 months - no consensus
    • Glucocorticoids for > 3 months
      • Prednisone < 7.5 mg/day: no consensus
      • Prednisone ≥ 7.5 mg/day: alendronate, risedronate, or teriparatide




IOM recommended dietary vitamin D allowance
Age Vitamin D (IU/day)
19 - 70 years 600 IU
> 70 years 800 IU




IOM recommended dietary calcium allowance
Age Sex Calcium (elemental)
mg/day
0 - 6 months M/F 200
6 - 12 months M/F 260
1 - 3 years M/F 700
4 - 8 years M/F 1000
9 - 18 years M/F 1300
19 - 50 years M/F 1000
51 - 70 years M 1000
51 - 70 years F 1200
≥ 71 years M/F 1200

Calcium content of common foods
Food Calcium (mg)
Milk (8 oz) 300 mg
Yogurt (6 oz) 300 mg
Cheese (1 oz or cubic in.) 200 mg
Fortified foods 80 - 1000mg
(varies widely)

Calcium supplement % elemental calcium Other
Calcium carbonate (ex. Caltrate®) 40%
  • Cheap, most common
  • Absorption is better with food
  • Absorption is decreased with acid-reducing
    meds (e.g. H2 blockers, PPIs)
Calcium citrate (ex. Citracal®) 21%
  • More expensive; requires more pills
  • Absorbed well with or without food
  • Acid-reducing meds (e.g. H2 blockers, PPIs)
    do not decrease absorption
Calcium lactate 13%
  • Often used as a food additive
Calcium gluconate (ex. Cal-Glu®) 9%
  • Typically given intravenously
  • Also available in oral form