Osteoporosis Case File

Osteoporosis Case File

Eugene C. Toy MD, Donald Briscoe, MD, FA  AFP, Bruce Britton, MD, Joel J. Heidelbaugh, MD, FA  AFP, FACG

Case 58

A 62-year-old Asian woman who is new to your office presents complaining of moderate right-sided chest pain and difficulty breathing deeply after she accidentally stumbled and fell against a railing while walking home with her husband the previous day. She states that she has had no significant medical concerns or hospitalizations and is taking no medications or supplements. Her parents died of "old age" in their 90s, and her siblings and children are in excellent health. She does not drink or smoke, has lactose intolerance, is a vegetarian, and exercises occasionally by walking. She has been feeling well recently and has an unremarkable review of systems. On examination, her body mass index (BMI) is 19.5 kg/m², blood pressure is 108/75 mm Hg, pulse is 72 beats/min, and respiratory rate is 15 breaths/min. The general, head, ears, eyes, nose, throat (HEENT), neck, heart, abdominal, and extremity examinations are all unremarkable. The chest examination reveals normal lung sounds bilaterally but inspiration is limited secondary to pain. There is significant point tenderness and a moderate-sized bruise in the right anterior and lower ribs where she injured herself. Pulse oximetry is 97%. Electrocardiogram (ECG) reveals normal sinus rhythm without abnormality. Chest and rib radiographs reveal a nondisplaced fracture of the anterolateral right ninth rib at the site of injury.

⯈ What additional diagnoses should be considered?

⯈ What is the most likely underlying cause?

⯈ What would be your next steps in evaluation and treatment?

ANSWER TO CASE 58

Osteoporosis

Summary: A 62-year-old woman presents with a fractured rib after a low-velocity trauma. She has a below-normal BMI and is of Asian ethnicity. She has no signs of cardiopulmonary compromise and appears clinically stable other than moderate pain.

• Additional diagnoses that should be considered: Underlying causes of pathologic fracture
• Most likely underlying cause: Osteoporosis
• Next steps: Incentive spirometry, pain management, and evaluation for pathologic fractures that include primary osteoporosis and secondary causes including chronic systemic diseases, endocrine disorders, metabolic disorders, malignancies, adverse drug effects (ADEs), and nutritional deficiencies

ANALYSIS

Objectives

1. Identify the risk factors and secondary causes of osteoporosis.
2. Understand the indications and recommendations for screening of osteoporosis in women and men.
3. Describe a rational evaluation for osteoporosis.
4. List the nonpharmacologic and pharmacologic options for prevention and management of osteoporosis.

Considerations

This 62-year-old female patient presents with a rib fracture from a low-impact trauma. Her age, ethnicity, weight, and dietary restrictions place her at an increased risk for developing osteoporosis. After preventing complications and treating pain for her rib fracture, assessment and management of the various causes of osteoporosis would significantly reduce this patient's risk for future fractures and disability associated with this disorder.

The evaluation of this patient should include a dual-energy x-ray absorptiometry (DEXA) scan. Considerations for laboratory testing to rule out secondary causes of osteoporosis should include serum alkaline phosphatase, calcium, and 25-hydroxy vitamin D. If there were other clinical symptoms or examination findings, additional testing of thyroid, liver, and kidney function tests to rule out hyperthyroidism, chronic liver disease, and renal insufficiency, respectively, should be considered. A complete blood count (CBC) could be considered if anemia, blood cell malignancy, or malabsorption syndromes are suspected.

Approach To:

Osteoporosis

DEFINITIONS

OSTEOPOROSIS: A low-density, mass, and structural deterioration of bone that leads to an increased risk of fracture. The World Health Organization (WHO) defines osteoporosis as "a hip or spinal mineral density (BMD) of 2.5 standard deviations or more below the T score (mean) for 'young normal' adult:' The Z score is the BMD compared with an average healthy individual of same gender and age. A Z score of less than or equal to -2.0 can be used with clinical signs in premenopausal women and men less than 50 years.

OSTEOPENIA: The WHO defines osteopenia as "a hip or spinal mineral density (T score) of 1.0 to 2.5 standard deviations below the mean for 'young normal' adult."

OSTEOMALACIA: A defect in bone mineralization that can lead to osteoporosis usually due to calcium or vitamin D deficiency.

CLINICAL APPROACH

PREVENTION

The National Osteoporosis Foundation (NOF) recommends that all men and women greater than 50 years should be counseled on risk of fractures from osteoporosis, be checked for possible secondary causes of osteoporosis, have adequate daily intake of calcium (1200 mg) and vitamin D (800-1000 IU), and perform regular weight-bearing exercises. Smoking cessation and alcohol reduction can further reduce risk. Additional pharmacologic options for preventive treatments that are Food and Drug Administration (FDA)-approved include hormone therapy, selective estrogen receptor blockers, and bisphosphonates. Due to cost and potential adverse drug effects, these medications are often reserved for those patients with high risk or DEXA scan evidence of significantly reduced bone density.

SCREENING

It is estimated that there are nearly 54 million people in the United States affected by osteoporosis and low bone mass, with 10.2 million diagnosed with osteoporosis (8.2 million women and 2 million men) and 43.4 million with osteopenia. If prevalence remains unchanged, it is estimated that 64.4 million people will be affected by 2020 and 71.2 million by 2030.

There are multiple recommendations for osteoporosis screening from medical societies and organizations across North America and Europe. The United States Preventive Services Task Force (USPSTF) recommends that all women aged greater than or equal to 65 and those less than 65 years with risk factors that are equal to or greater than the risk of a healthy 65-year-old Caucasian woman should be screened for osteoporosis. This 10-year risk is 9.3% based on the WHO's FRAX calculation tool (http:/ /www.shef.ac.uk/FRAX/). The USPSTF states that there is insufficient evidence to assess the balance of benefits and harms of screening for osteoporosis in men. The NOF recommends that all men aged 70 and older and those aged 50 to 69 with risk factors undergo screening. The preferred screening modality is via DEXA scan of the femoral neck and lumbar spine. Quantitative ultrasound densitometry and peripheral DEXA can predict risk, but do not correlate adequately to be used diagnostically.

DIAGNOSIS

Osteoporosis can be diagnosed radiographically or clinically. A central DEXA T score of -2.5 or more of the femoral neck and lumbar spine is the standard radiographic diagnostic test. Quantitative computed tomography absorptiometry is limited by cost and radiation exposure. A clinical diagnosis of osteoporosis can present with low-impact fractures (eg, a fall below standing height) or by spontaneous fractures due to bone fragility. Patients who present with these fractures should undergo thorough evaluation to rule out secondary causes of fracture.

Evaluating for Secondary Causes of Osteoporosis

In postmenopausal women, secondary causes of osteoporosis are presumed unusual and, in the absence of other symptoms, additional testing may not be indicated. However, approximately 50% of pre- and perimenopausal women, and men of any age, with osteoporosis may have a secondary cause. Common secondary causes include hyperthyroidism, primary hyperparathyroidism, vitamin D deficiency, amenorrheic conditions (eg, female athlete triad, anorexia), and chronic use of corticosteroids. Tobacco use and alcohol use of greater than two drinks per day are also significant risks. Serologic testing, including a complete blood count, kidney and liver function tests, serum calcium, thyroid-stimulating hormone (TSH), and 25-hydroxy vitamin D levels should be considered standard components of the workup for the patient with suspected or diagnosed osteoporosis. When appropriate, estradiol levels in women and testosterone levels in men can screen for hypogonadism, as there is a direct correlation between osteoporosis and menopause and testosterone deficiency/late-onset hypogonadism.

TREATMENT

Recommendation for treatment varies between organizations. The NOF recommends treatment for postmenopausal women and men aged 50 and older presenting with the following symptoms:

• Hip or vertebral fracture
• T score less than or equal to -2.5 at femoral neck or spine after appropriate evaluation to exclude secondary causes
• BMD T score -1.0 to -2.5 at femoral neck or spine and greater than or equal to 3 % 10-year risk of hip fracture and greater than or equal to 20% 10-year risk of major osteoporosis fracture based on the WHO FRAX algorithm (http://www.she£ac.uk/FRAX/)

Treatment should be considered in patients with elevated risks or BMD above and below these recommendations, and based on patient preferences. Nonpharmacologic treatments include fall prevention along with treatments to mitigate risks from impaired vision, balance, gait, cognitive impairment, and dizziness/vertigo. Smoking cessation and avoidance of excessive alcohol consumption should be encouraged. Home safety evaluations for hazards and durable medical equipment (eg, grab bars, walkers, etc) needs should be undertaken. Hip protectors and lumbar braces have not been shown to be effective in prevention of falls in patients with osteoporosis.

A universal recommendation in postmenopausal women and patients with osteoporosis is calcium and vitamin D intake supplementation; although in recent years the latter has become controversial. It is recommended that patients with osteoporosis consume at least 1200 mg of calcium a day in divided doses (no more than 500 mg per dose). A dose of at least 800 to 1000 IU of vitamin D should be used in conjunction with the calcium. In proven vitamin D deficiency, loading doses of ergocalciferol (vitamin D2) 50,000 IU weekly for 4-8 weeks is recommended, followed by maintenance dosing of 50,000 IU monthly or cholecalciferol (vitamin D3) 1000 to 2000 IU daily. The treatment goal serum level of 25-hydroxy vitamin D is greater than 30 ng/mL. The Institute of Medicine recommends against routine screening of vitamin D levels in the general population.

FDA-Approved Pharmacologic Therapy

Bisphosphonates

Oral bisphosphonates are the first-line agent for treatment of osteoporosis. Alendronate, risedronate, and ibandronate inhibit osteoclastic activity and have antiresorptive properties. These medications have excellent evidence for reduction in fractures in the hip and spine. Depending on the agent, they can be dosed daily, weekly, or monthly. Intravenous bisphosphonates can be given four times a year (ibandronate) or yearly (zoledronic acid). Oral agents must be taken on an empty stomach with a full glass of water and the patient must stay in an upright or standing position for at least 30 minutes after dosing due to a risk of esophagitis. The optimal length of treatment continues to be debatable, as there are concerns about atypical bone fractures in patients taking bisphosphonates for 5 years or greater. There are also rare reported cases of osteonecrosis in the jaw (mostly with IV bisphosphonates in cancer patients) after dental procedures.

Hormone Replacement Therapy and SERMs

Estrogen replacement is FDA-approved for prevention of osteoporosis in women with significant menopausal vasomotor symptoms, yet this recommendation is fraught with controversy due to the increased risks of thrombosis and breast cancer. It should be used at the lowest effective dose and for the shortest possible duration. Women taking estrogen and who have not had a hysterectomy should also take progesterone to limit the risk of endometrial cancer. Raloxifene, a selective estrogen receptor modulator (SERM), is FDA-approved for prevention and treatment of osteoporosis, especially of the lumbar spine. Raloxifene has been shown to reduce the risk of breast cancer, yet increases vasomotor symptoms and risk of deep venous thrombosis. T his medication may be best reserved for postmenopausal women who do not tolerate bisphosphonates, who do not have vasomotor symptoms, and who have a high risk for development of breast cancer.

Calcitonin

Calcitonin is an antiresorptive medication that is administered as a nasal spray. It has evidence for prevention of vertebral compression fracture reduction as well as a modest analgesic effect. It is considered as a second-line agent, as more effective medications are available.

Teriparatide

Teriparatide is a recombinant human parathyroid hormone that causes bone density growth through its effect on osteoblasts. It is administered as a daily subcutaneous injection for up to 2 years. Because of its osteoblastic activity, it is contraindicated in patients at risk for osteosarcoma, such as patients with Paget disease, a history of bone radiation, or unexplained elevated serum alkaline phosphatase levels (which can be fractionated via isoenzymes to discern origin of tissue). It is approved for patients with severe osteoporosis and in those who have not benefited from or cannot tolerate bisphosphonates.

Denosumab

Denosumab was approved by the FDA in June 2010 for women with severe risk of osteoporotic fracture who are intolerant of bisphosphonates. It is a monoclonal antibody that prevents osteoclast differentiation and limits bone turnover. It has evidence in prevention of all forms of osteoporotic fractures and has similar efficacy to bisphosphonates. Denosumab is given as a subcutaneous injection once every 6 months and has a warning of increased risk of serious infection due to its immunosuppressive properties.

Combination Therapy

Combining bisphosphonates with other agents has not been well studied, the cost may be prohibitive, and the potential for adverse drug effects is unknown.

Monitoring of Treatment Success

Little evidence is available to indicate how often and what kind of follow-up testing is needed for monitoring effectiveness of treatment for osteoporosis. The NOF recommends repeat BMD testing every 2 years. Biochemical markers of bone turnover can be used early on to assess effectiveness of treatment, but are of limited usefulness due to biological and laboratory variability. Reduced BMD after treatment usually indicates patient compliance issues, but could indicate inadequate calcium and vitamin D intake, an undiagnosed secondary cause of osteoporosis, or treatment failure.

COMPREHENSION QUESTIONS

58.1 According to USPSTF guidelines, which of the following patients should be routinely screened for osteoporosis via DEXA scan?

A. A 65-year-old African-American man who takes hydrochlorothiazide for hypertension

B. A 53-year-old postmenopausal Caucasian woman who takes hormone replacement therapy for hot flashes

C. A 67-year-old Caucasian woman who takes 1500 mg of calcium and 800 IU of vitamin D daily

D. A 45-year-old Asian woman who broke her hip by falling off of a ladder while cleaning her gutters

E. A 55-year-old African-American woman who used inhaled steroids for 10 years for the management of asthma, but who never took oral steroids

58.2 A 60-year-old woman presents for follow-up for a wrist fracture that she sustained when she tripped while walking her dog. Follow-up DEXA scanning revealed a T score of -2.9. She has been postmenopausal for 10 years and has not had a hysterectomy. Which of the following interventions is most appropriate for reducing her risk of subsequent osteoporosis-related fractures?

A. Daily exercise

B. Estrogen replacement therapy

C. Vitamin D and calcium supplementation with a follow-up DEXA in 2 years

D. Alendronate

E. Calcitonin

58.3 A 51-year-old newly menopausal, physically active woman of mixed AsianEuropean origin presents inquiring about bone density testing. Her BMI is 20.9 kg/m2; she has a history of lactose intolerance and a 15-year use of low-dose inhaled corticosteroids for allergy-induced asthma. She has no history of fracture, oral steroid use, heavy alcohol use, or smoking. Based on the USPSTF and NOF recommendations and FRAX calculations (http://www.shef.ac.uk/FRAX/), which of the following statements is true for this patient?

A. Her risk as an Asian is greater than her risk as a Caucasian.

B. DEXA scanning is recommended.

C. Inhaled steroids significantly increase her risk of osteoporosis.

D. Calcium and vitamin D supplementation is recommended.

E. Low-dose bisphosphonate therapy is recommended.

ANSWERS

58.1 C. The USPSTF recommends routine osteoporosis screening for women 65 years or older without previous known fractures or secondary causes of osteoporosis. They also recommend routine screening for women less than 65 years whose 10-year fracture risk is greater than or equal to that of a 65-year-old white woman with no additional risk factors. A hip fracture that occurred with a significant traumatic injury would not be an indication for bone density screening, but a hip fracture associated with a minor injury, such as falling from a standing position, would be. Inhaled steroids are not considered a risk factor for osteoporosis.

58.2 D. This patient meets the criteria for the diagnosis of osteoporosis. Supplementation with calcium and vitamin D along with weight-bearing exercise are appropriate but not likely, by themselves, to increase her bone density sufficiently to reduce her fracture risk. Bisphosphonates, such as alendronate, are the first-line treatment in this situation based on their effectiveness at reducing fracture risk. Estrogen therapy alone is not recommended in women with an intact uterus, as there is an increased risk of endometrial cancer. Calcitonin would be reserved for consideration in a patient who does not tolerate or has contraindications to the use of bisphosphonates.

58.3 D. Calcium of at least 1200 mg/d and vitamin D of at least 800 IU/d is a universal recommendation for menopausal women. The FRAX calculator shows that Caucasian and Asian women in the United States have a 10-year risk of 4.5% and 3.3%, respectively. DEXA scans for screening are recommended by USPSTF when women aged 50 to 64 have a 10-year risk of 9.7% or greater. Low-dose inhaled steroids are not associated with significantly increased risk of osteoporosis.

CLINICAL PEARLS

⯈ Calcium supplementation is considered a universal recommendation for prevention and treatment of osteoporosis in postmenopausal women. The outcomes data on benefit for vitamin D supplementation remain controversial but the risk of harm is limited .

⯈ The DEXA scan is considered as the diagnostic test of choice for both screening and diagnosis of osteoporosis and osteopenia .

⯈ There is no universal agreement on screening for osteoporosis in men, but if a male patient has significant risk factors, screening should be conducted since approximately 20% of patients with osteoporosis are men .

⯈ Vitamin D deficiency and heavy alcohol consumption are common secondary causes of decreased BMD and osteoporosis.

REFERENCES

Gourlay ML, Fine JP, Preisser JS, et al. Bone-density testing interval and transition to osteoporosis in older women. N Engl] Med. 2012:366:225-233. 

Lindsay R, Cosman F. Osteoporosis. In: Kasper D, Fauci A, Hauser S, et al., eds. Harrison's Principles of Internal Medicine. 19th ed. New York, NY : McGraw-Hill Education; 2015. Available at: http:// accessmedicine.mhmedical.com. Accessed May 25, 2015. 

National Osteoporosis Foundation. Clinician's Guide to Prevention and Treatment of Osteoporosis. Washingron, DC: National Osteoporosis Foundation; 2010. 

Prockop DJ. New targets for osteoporosis. N Engl] Med. 2012:367:2353-2354. 

Rao SS, Budhwar N, Ashfaque A. Osteoporosis in men. Am Fam Physician. 2010:82(5):503-508. 

Sweet M, Sweet J, Jeremiah M, Galazka S. Diagnosis and treatment of osteoporosis. Am Fam Physician. 2009:79(3):193-200. 

U.S. Preventive Services Task Force. Screening for osteoporosis: recommendation statement. Am Fam Physician. 2011:83(10):1197-1200.

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