Osteoporosis is a significant chronic condition worldwide, causing morbidity and mortality that may be prevented with mitigation of risk factors, screening, and treatment of low bone density to prevent fractures. Adequate intake of calcium and vitamin D as well as regular weight-bearing exercise are integral for optimal bone health. Decreased bone density on dual-energy x-ray absorptiometry screening or evidence of fragility fractures are qualifiers for treatment. Treatment options beyond the first-line treatment of oral bisphosphonates exist for those who do not tolerate these medications or for those who require intensified regimens due to very high risk of fracture.
Key points
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Clinicians should focus on bone health across the lifespan as almost 50% of women in the United States will sustain an osteoporotic fracture.
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To support bone health, recommend adequate calcium, vitamin D, and physical activity and avoidance of tobacco and alcohol use.
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Bone density testing should begin at age 65 for most women, and earlier for those at higher risk for osteoporosis.
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Once identified by bone density testing or history of fragility fracture, osteoporosis evaluation should include a laboratory evaluation to look for causes of secondary osteoporosis.
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Oral bisphosphonates are the first-line treatment for osteoporosis.
Article
Definition
Osteoporosis is a condition of decreased bone mass and altered bone architecture that results in weakened bones. This weakening increases risk for fracture with resultant morbidity and mortality. ,
Pathophysiology
Osteoporosis is characterized by loss of bone mass through architectural deterioration on a microscopic level, which can be measured by a dual-energy x-ray absorptiometry (DEXA) scan to measure bone density at the femoral neck, lumbar spine, and sometimes the distal radius. Bone strength is affected by the bone turnover rate—the rate at which old bone is resorbed and new bone is created. These factors that determine bone quality mean that older women are particularly vulnerable to osteoporosis since menopause-related decreases in estrogen levels increase bone resorption and decrease new bone formation.
Osteoporosis is diagnosed when bone density is 2.5 or more standard deviations below that of a young adult (T score). Less severe bone loss, or osteopenia, is defined as bone density ranging between 1 and 2.5 standard deviations below that of a young adult. In both cases, fracture risk increases as bone loses density and strength.
Epidemiology
Worldwide, osteoporosis is thought to affect over 200 million women with osteoporotic fractures causing significant pain, morbidity, and mortality. One-year mortality post hip fracture is estimated to be as high as 14% to 58%, with significant burden to finances and independence even to those who thrive clinically. Of the 10 million people in the United States who have osteoporosis, approximately 80% are women, and approximately half of American women older than age 50 will break a bone due to osteoporosis. In the United States, the cost of osteoporosis-related fracture treatment and resultant care needs is estimated at $17.9 billion annually.
Presentation
Hip fractures, vertebral fractures, and distal forearm fractures are the most common types of osteoporotic fractures, often occurring after simple mechanical falls. Screening is particularly important because many women do not become aware that they have osteoporosis until they experience a fracture.
Osteoporosis Screening
Newly updated US Preventive Services Task Force guidelines recommend screening for osteoporosis using bone density testing in all women age 65 and over as well as postmenopausal women under age 65 who are at increased risk for an osteoporotic fracture (grade B recommendations). The level of risk for women under age 65 should be determined using a formal clinical risk assessment tool such as the fracture risk assessment tool (FRAX) fracture risk assessment tool. , There are no consistent guidelines for screening transgender patients.
Good quality evidence to inform screening and follow-up intervals for bone density testing is lacking. For patients on osteoporosis treatment, expert recommendations suggest repeating DEXA after 1 year of initiating medication therapy and after 1 year of changing medication therapy. In those not qualifying for treatment, the American College of Preventive Medicine and the American Academy of Family Physicians (AAFP) Choosing Wisely Campaign recommend bone density screening no more frequently than every 2 years while the National Osteoporosis Foundation and the Bone Health and Osteoporosis Foundation recommend screening every 2 years
Data from a single cohort study of 4,957 women age 67 and older indicate that consideration should be given to adjusting screening intervals based on a woman’s bone density on initial screening. This study found that in women with normal bone density or mild osteopenia on initial testing, osteoporosis would develop in just 10% of postmenopausal women over 15 years. For women with moderate osteopenia and advanced osteopenia, this 10% threshold was reached at 5 years and 1 year, respectively.
Indications for early screening for osteoporosis are outlined in Box 1 .
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All postmenopausal women:
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With a history of fracture(s) without major trauma
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With osteopenia identified radiographically
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Starting or taking long-term systemic glucocorticoid therapy (≥3 months)
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Other perimenopausal or postmenopausal women with risk factors for osteoporosis if willing to consider pharmacologic interventions:
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BMI <20 kg/m 2
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Family history of osteoporotic fracture
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Premature menopause
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Current smoking status
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Alcohol use >2 drinks/day
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For postmenopausal women, lower T scores correlate with higher fracture risk. For premenopausal women, a Z score is reported which is a measure of the difference between the patient’s bone density and an average bone density of healthy age, sex, and ethnicity matched peers.
The American Association of Clinical Endocrinologists/American College of Endocrinology Clinical Practice (AACE/ACE) recommends pharmacologic treatment for people who are in 1 of 3 categories: those with osteopenia and history of a fragility fracture of the hip or spine; those with T score −2.5 even in absence of fracture history; and those with T score −1.0 to −2.5 with 10-year FRAX probability of major osteoporotic fracture greater than 20% or hip fracture greater than 3% with other groups setting forth similar recommendations. Tools for shared decision-making can be used to facilitate an informed discussion about risks and benefits of treatment with patients using graphical models that represent the impact of treatment decisions based on the patients’ own fracture risk data. , Clinicians should be aware that the FRAX tool has received some criticism for underestimating fracture risk in minoritized people and thus creating risk for undertreatment of osteoporosis in these patients.
Osteoporosis evaluation
Patients who have osteoporosis should have a comprehensive evaluation looking for modifiable risk factors and medical conditions that affect bone health.
History and Physical
The clinician should ask about prior fractures and how they were sustained. Low-impact (fragility) fractures are fractures that occur due to a fall from standing height or less, or a similar force, excluding fractures of the face, skull, fingers, and toes. Low-impact injuries generally would not be expected to cause a fracture in normal bone. A history of height loss, kyphosis, or spinal tenderness on examination suggests the possibility of vertebral fractures that may not have previously come to clinical attention. The history should identify risk factors for low bone density including smoking, excessive alcohol intake (3 or more drinks per day), early menopause, and a family history of osteoporosis. It is also important to assess fall risk using validated tools such as those described in the Centers for Disease Control and Prevention Stopping Elderly Accidents, Deaths & Injuries (CDC STEADI) algorithm, and to assess gait, lower extremity strength, and balance as contributors to fall risk and therefore fracture risk. The history and physical examination should look for medical conditions and medications that can cause osteoporosis, and comorbidities that could affect osteoporosis treatment decisions (see Box 1 ), including a history of chronic kidney disease, dental disease, gastroesophageal reflux disease, and esophageal disease.
Medications and medical conditions that contribute to osteoporosis are listed in Table 1 .
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Laboratory Evaluation
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The AACE/ACE Clinical Practice Guideline , recommends the following laboratory evaluation for people with osteoporosis:
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Complete blood count
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Comprehensive metabolic panel (including electrolytes, calcium, total protein, albumin, liver enzymes, alkaline phosphatase)
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Phosphate
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Serum 25-hydroxy vitamin D
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Serum parathyroid hormone
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24-hour urine collection for calcium, sodium, and creatinine—collect once patient has adequate vitamin D levels and calcium intake for at least 2 weeks
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Additional tests if clinically indicated:
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Serum thyroid stimulating hormone (patients on thyroid hormone replacement or with symptoms of thyroid disease)
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Tissue transglutaminase antibodies (for suspected celiac disease)
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Serum protein electrophoresis and free kappa and lambda light chains (for suspected myeloma)
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Imaging
Only about 23% of vertebral fractures seen on plain radiographs come to clinical attention. These often clinically silent fractures can lead to a diagnosis of osteoporosis in patients with T-scores greater than −2.5 and can affect treatment decisions. Vertebral fracture can be diagnosed with spine x-rays or by adding vertebral fracture analysis to DEXA testing. The AACE/ACE Clinical Practice Guideline recommends imaging in patients with T-scores <−1.0 and one or more of the following:
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Women aged ≥ 70 and men aged ≥ 80
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Historical height loss >4 cm (>1.5 inches)
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Self-reported but undocumented prior vertebral fracture
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Glucocorticoid therapy equivalent to ≥ 5 mg of prednisone or equivalent per day for ≥ 3 months
Imaging can also be considered in patients with unexplained height loss or back pain, kyphosis, and a history of systemic glucocorticoid therapy not meeting the above criteria.
Recommendations to optimize bone health and decrease fracture risk
Combined Calcium and Vitamin D Supplementation
Combined calcium and vitamin D supplementation has been shown to reduce fracture risk in higher risk populations. A meta-analysis of randomized controlled trials that included community dwelling and institutionalized adults showed that combined calcium and vitamin D supplementation significantly reduced overall fracture risk by 15% and hip fracture risk by 30%. In the included trials, participants received vitamin D3 at doses of 400 to 800 international units (IU) daily and calcium at doses of 500 to 1200 IU daily and were followed for 1 to 7 years. A Cochrane review of studies of vitamin D supplementation in postmenopausal adults found no benefit of vitamin D supplementation alone, but did find a statistically significant 5% reduction in overall fracture risk and 16% reduction in hip fracture risk with combined calcium and vitamin D supplementation. This effect was greater in institutionalized participants, with a 15% reduction in overall fracture risk and a 25% reduction in major fracture risk. Current evidence does not show that calcium and vitamin D supplementation increases bone density or reduces fracture risk in healthy premenopausal women. A small body of evidence shows that combined calcium and vitamin D supplementation prevents bone loss in people taking long-term glucocorticoids, who are at high risk for decreasing bone density. The recommended daily calcium and vitamin D intake for adults is shown in Table 2 .
| Age/Sex | Recommended Calcium Intake (mg/day) | Calcium Safe Upper Limit | Recommended Vitamin D Intake (mcg/day) | Vitamin D Safe Upper Limit (mcg/day) |
|---|---|---|---|---|
| 19–50 (M + F) | 1000 | 2500 | 15 | 100 |
| 51–70 (M) | 1000 | 2000 | 15 | 100 |
| 51–70 (F) | 1200 | 2000 | 15 | 100 |
| 71+ (M + F) | 1200 | 2000 | 20 | 100 |
Vitamin D supplementation
AACE/ACE guidelines recommend measuring 25-hydroxyvitamin D levels in patients who are at risk for vitamin D deficiency, especially people with osteoporosis and supplementing with vitamin D 1000 to 2000 IU to maintain 25-hydroxyvitamin D levels between 30 and 50 ng/mL in people with osteoporosis. There is some concern that doses of vitamin D3 of 4000 IU daily or greater, or intermittent high-dose supplementation may not be beneficial, and some studies suggest it may actually worsen bone density and increase fall and fracture risk.
Vitamin D3 is about 3 times more potent than equivalent doses of vitamin D2, so vitamin D3 is usually preferred; however, it may be easier to find vegetarian and vegan sources of vitamin D2 than D3. , Both can be monitored using a total 25-hydroxyvitamin D level; however some lab tests under detect vitamin D2, so consider checking 25-hydroxyvitamin D2 in patients taking D2 supplements.
With vitamin D supplementation, there is a risk of mild hypercalcemia, gastrointestinal symptoms, hypercalciuria, and kidney stones, especially at higher doses. The optimal interval for rechecking vitamin D levels is not known, but some suggest rechecking in about 8 weeks. https://www.nejm.org/doi/10.1056/NEJMra070553?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub0pubmed . ,
Calcium Supplementation
Sufficient calcium intake across the lifespan is important for bone health. Guidelines recommend a dietary intake of calcium totaling 1,200 mg/day for women older than 50. Women should be encouraged to eat a variety of calcium-rich foods. Taking a dietary calcium inventory ( Table 3 ) can help determine calcium intake from diet and can serve as a tool for educating patients about how to meet the recommended daily intake of calcium with calcium-rich foods.
| Food | Calcium Per Serving (mg) | Number of Servings | Total Calcium (mg) |
|---|---|---|---|
| General diet | 250 | ||
| Milk (8 oz) | 300 | x _____ = | |
| Soy/almond milk (8 oz) | 450 | x _____ = | |
| Yogurt, plain (8 oz) | 450 | x _____ = | |
| Yogurt, greek, plain (8 oz) | 250 | x _____ = | |
| Yogurt, soy, plain (8 oz) | 300 | x _____ = | |
| Cheese (1 oz) | 200 | x _____ = | |
| Tofu, prepared with calcium (½ cup) | 430 | x _____ = | |
| Orange juice, calcium fortified (8 oz) | 450 | x _____ = | |
| Sardines, canned (3 oz) | 325 | x _____ = | |
| Collard greens/spinach (1 cup) | 250 | x _____ = |
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