What are the recommendations for screening and treatment of osteoporosis?

Screening for Osteoporosis

Who to Screen

Screen all women aged 65 years or older with dual-energy x-ray absorptiometry (DXA) of the hip and lumbar spine. 1, 2

Women Under Age 65

• Screen postmenopausal women younger than 65 years whose 10-year fracture risk equals or exceeds that of a 65-year-old white woman with no additional risk factors (9.3% 10-year fracture risk). 1, 2
• Use the FRAX tool (available at www.shef.ac.uk/FRAX/) to calculate 10-year fracture risk for women aged 50-64 years. 1, 2
• The single best predictor of low bone mineral density is body weight less than 70 kg, which should trigger screening consideration in younger postmenopausal women. 1
• Other risk factors warranting screening include: previous fracture, parental history of hip fracture, glucocorticoid use, rheumatoid arthritis, secondary osteoporosis causes, excessive alcohol consumption, and smoking. 2

Men

For men, there is insufficient evidence to recommend routine screening. 1, 2 However, the National Osteoporosis Foundation recommends screening all men aged 70 years or older, and the American College of Physicians recommends assessing older men for risk factors and screening those at increased risk who are candidates for drug therapy. 1, 2

• Men most likely to benefit from screening have a 10-year fracture risk equal to or greater than that of a 65-year-old white woman without risk factors (9.3%). 1

Screening Method

DXA of the hip and lumbar spine is the gold standard for osteoporosis screening and diagnosis. 1, 2 Quantitative ultrasonography of the calcaneus can predict fractures as effectively as DXA, but current diagnostic and treatment criteria rely exclusively on DXA measurements. 1

Screening Intervals

Evidence is lacking about optimal intervals for repeated screening. 1 A minimum of 2 years is needed to reliably measure a change in bone mineral density due to testing precision limitations, though longer intervals may be adequate. 1 One study found that repeated BMD measurement after 8 years was not more predictive of fracture risk than the original measurement. 1

Treatment Recommendations

Who to Treat

Treat women with osteoporosis (T-score ≤ -2.5) or those with a fragility fracture. 3 Treatment decisions should prioritize absolute fracture risk rather than BMD alone. 2

First-Line Pharmacotherapy

Bisphosphonates are the first-line treatment for postmenopausal women with osteoporosis. 1, 4 The evidence is strongest and most consistent for bisphosphonates and raloxifene in reducing vertebral fractures. 1

• Bisphosphonates reduce vertebral fractures by 34% (RR 0.66,95% CI 0.50-0.89) in primary prevention trials. 1
• Bisphosphonates show a non-statistically significant trend toward reducing nonvertebral fractures (RR 0.83,95% CI 0.64-1.08). 1
• In the Fracture Intervention Trial, alendronate significantly reduced fractures only in women with baseline femoral neck T-scores less than -2.5. 1

Alternative Agents

• Raloxifene reduces vertebral fractures by 39% (combined RR 0.61,95% CI 0.55-0.69) compared with placebo. 1
• Parathyroid hormone, estrogen, and calcitonin have also been shown to reduce vertebral fractures in postmenopausal women. 1
• For patients at very high risk or with previous vertebral fractures, consider anabolic agents (teriparatide, abaloparatide, romosozumab) as initial therapy. 3, 4

Treatment in Men

Evidence for osteoporosis treatment in men is limited. 1 There are no primary prevention trials of bisphosphonates in men, only two secondary prevention trials of alendronate. 1 In pooled analysis, alendronate reduced vertebral fractures (OR 0.35,95% CI 0.17-0.77) but did not significantly reduce nonvertebral fractures. 1

Medication Administration

For alendronate, instruct patients to: 5

• Take with a full glass of plain water (6-8 ounces) first thing upon arising, at least 30 minutes before any food, beverage, or other medication
• Remain upright (not lie down) for at least 30 minutes after taking the medication
• Not chew or suck on the tablet to avoid oropharyngeal ulceration

Adjunctive Measures

All patients with osteoporosis should receive: 1

• Adequate calcium and vitamin D supplementation
• Weight-bearing and resistance-training exercise
• Smoking cessation counseling
• Moderation of alcohol intake
• Fall prevention strategies

Important Caveats

Harms of Screening and Treatment

The harms of screening are small and consist primarily of false-positive results causing unnecessary treatment, false-negative results, patient anxiety, and opportunity costs. 1, 2

For bisphosphonates, the harms are no greater than small. 1 Serious gastrointestinal adverse events are not definitively increased. 1 However, patients should be counseled about potential risks including esophageal irritation, osteonecrosis of the jaw (particularly with dental procedures), and atypical femoral fractures. 6, 5

For denosumab, serious risks include: 6

• Severe jaw bone problems (osteonecrosis)
• Unusual thigh bone fractures
• Increased risk of multiple spine fractures after stopping treatment
• Serious infections
• Severe hypocalcemia (especially in patients with kidney disease)

Treatment Duration Considerations

Osteoporosis is not cured by treatment—skeletal deterioration resumes when medication is discontinued. 7 The diagnosis of osteoporosis persists even if subsequent DXA T-scores improve above -2.5. 7 Benefits of treatment emerge 18-24 months after initiation. 1

Common Pitfalls

• 41.3% of women undergoing DXA screening do not meet criteria for testing, representing inappropriate use of resources. 8
• Among women with indications for treatment, 35.3% are not receiving therapy, while 17.8% without indications are inappropriately treated. 8
• African-American women have higher average bone mineral density than white women at any given age and are less likely to benefit from screening. 1