OSTEOPOROSIS













  • Reference [1,2]
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






  • Reference [3,4]
USPSTF osteoporosis screening recommendations
Women
  • ≥ 65 years: screen all women
  • Postmenopausal women < 65 years: screen women who are at increased risk of osteoporosis, as determined by a formal clinical risk assessment tool. The USPSTF recommendations do not provide specific guidance on the degree of increased risk that warrants testing. They provide an example that says if a woman's 10-year risk of major osteoporotic fracture is greater than that of an average-risk 65 year-old woman, then testing is justified. In the U.S., the 10-year fracture risk of an average-risk 65 year-old woman is 8.4% using the FRAX tool.
  • The preferred screening method is DXA scanning
Men
  • Insufficient evidence to recommend screening
Endocrine Society osteoporosis screening recommendations in men
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)
  • The preferred screening method is DXA scanning


  • Intervals are from adjusted analysis
  • Reference [7]
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)




  • Reference [1,2]
Classification criteria for BMD T-scores
Category T-score
Normal -1 or above
Osteopenia -1.0 to -2.5
Osteoporosis -2.5 or below

  • Z-scores are recommended in premenopausal women, men < 50 years of age, and children
  • Reference [2]
Classification criteria for Z-scores
Category Z-score
Within expected range greater than -2.0
Below expected range for age -2.0 and below




  • Reference [1,2]
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

  • Reference [1,2]
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
  • D - American College of Physicians recommendation
  • Reference [1,2,4]
Osteoporosis treatment recommendations for postmenopausal women and men age 50 years and older
WHO TO TREAT
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
Women
    First line:
    • Alendronate (Fosamax®)
    • Risedronate (Actonel®)
    • Zoledronic acid (Reclast®)
    • Denosumab (Prolia®) [B,D]
    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]
    The ACP recommends against using menopausal estrogen therapy or menopausal estrogen plus progestin therapy or raloxifene for the treatment of osteoporosis in women
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 by the IOF [A]
  • The ACP 2017 OP guidelines recommend against BMD testing during the 5-year pharmacologic treatment period [D]
THERAPY DURATION
IOF recommendation
  • 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]
ACP recommendation
  • Treat women with OP with pharmacologic therapy for 5 years. Do not perform BMD testing during the 5-year treatment period. [D]


  • Increase the risk generated with FRAX by 1.15 for major osteoporotic fracture and 1.2 for hip fracture
  • Reference [12]
ACR recommendations for treatment and prevention of glucocorticoid-induced OP.
Recommendations are for patients receiving long-term glucocorticoids defined as ≥ 2.5 mg/day for ≥ 3 months.
ASSESSING RISK (WHEN TO ORDER BMD TESTING)
Initial testing
  • Adults < 40 years old
    • History of OP fracture OR any of the following: malnutrition, significant weight loss or low body weight, hypogonadism, secondary hyperparathyroidism, thyroid disease, family history of hip fracture, history of alcohol use ( ≥ 3 units/day) or smoking
      • BMD test within 6 months of starting GCs
    • No risk factors
      • No BMD testing
  • Adults ≥ 40 years old
    • FRAX with GC dose correction and BMD testing within 6 months of starting GC treatment

Follow-up testing
  • In general, the recommendations state that patients with any risk factor for OP should have BMD testing every 2 - 3 years
WHO TO TREAT
Adults < 40 years old
  • Any of the following present:
    • History of OP fracture
    • Z score < -3 at hip or spine and prednisone ≥ 7.5 mg/day
    • > 10%/year loss of BMD at hip or spine and prednisone ≥ 7.5 mg/day
    • Very high dose GC (prednisone ≥ 30 mg/day and cumulative dose of > 5 grams) and ≥ 30 years old

Adults ≥ 40 years old
  • Any of the following present:
    • History of OP fracture
    • Men ≥ 50 years and postmenopausal women with a T-score ≤ -2.5 at the hip or spine
    • GC-adjusted FRAX 10-year risk for major osteoporotic fracture ≥ 10%
    • GC-adjusted FRAX 10-year risk for hip fracture > 1%
    • Very high dose GC (prednisone ≥ 30 mg/day and cumulative dose of > 5 grams)
TREATMENT CHOICE
Women of childbearing potential:
  • Treat with the following:
    • First-line therapy: Oral bisphosphonate
    • Second-line therapy: Teriparatide
    • All patients should receive calcium 1000 - 1200 mg/day and vitamin D 600 - 800 IU/day (maintain serum level ≥ 20 ng/ml)

Women not of childbearing potential and men:
  • Treat with the following:
    • First-line therapy: Oral bisphosphonate
    • Second-line therapy: IV bisphosphonates
    • Third-line therapy: Teriparatide
    • Fourth-line therapy: Denosumab
    • All patients should receive calcium 1000 - 1200 mg/day and vitamin D 600 - 800 IU/day (maintain serum level ≥ 20 ng/ml)




  • Reference [2]
IOM recommended dietary vitamin D allowance
Age Vitamin D (IU/day)
19 - 70 years 600 IU
> 70 years 800 IU




  • Dosage in terms of elemental calcium
  • Reference [1]
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

  • Reference [2]
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 - 1000 mg
(varies widely)

  • For doses > 500 mg/day, give in divided doses to improve absorption
  • Reference [2]
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