Learning objective
- •
The integration of clinical findings, DXA scan results, FRAX scores, and National Osteoporosis Foundation guidelines to individualize the management strategy for patients with densitometric evidence of osteopenia and/or high falls/fracture risks.
The case study
Reasons for seeking medical help
- •
AC is concerned about having osteoporosis because of her positive family history: both her mother and grandmother had osteoporosis. Her mother has pronounced kyphosis and her grandmother died a few weeks after sustaining a hip fracture.
- •
AC had a DXA scan done about 2 weeks prior to her present encounter. It showed evidence of osteopenia: lowest T-score in the upper four lumbar vertebrae: −1.8.
Past medical and surgical history
- •
No relevant medical or surgical history.
- •
Menarche at age 12 years, regular menstrual periods.
- •
Menopause at age 50 years, no hormonal replacement therapy.
Lifestyle
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Exercises regularly three times a week: goes to a fitness center and does a combination of aerobic and resistance exercises. Each session lasts about 60 min. In addition, she often plays tennis: at least 1 h, during weekends.
- •
Drinks daily at least two 8-oz glasses of milk and one glass of orange juice fortified with calcium. She also has a cup of yogurt every day and regularly eats dairy products. She has done so for as long as she can remember.
- •
Does not smoke cigarettes, never did.
- •
Consumes alcoholic drinks only in moderation, not exceeding 3 drinks a week.
- •
Drinks neither caffeinated, nor soda drinks.
Family history
Positive for osteoporosis:
- •
Mother has pronounced kyphosis.
- •
Grandmother died after sustaining a hip fracture.
Medication(s)
- •
Multivitamin tablets, 1 daily.
Clinical examination
- •
Denies any history of falls, near-falls, or dizzy spells.
- •
Weight: 130 pounds, height 5′5″, arm span 65″.
- •
No relevant significant clinical findings.
Laboratory result(s)
About 4 weeks prior to her visit, she had a number of laboratory tests done as part of her annual physical examination. All results were within the normal limits, including complete blood count (CBC), comprehensive metabolic panel (CMP), serum 25-hydroxy-vitamin D, and thyroid stimulating hormone (TSH).
| Region | BMD | T-score |
|---|---|---|
| Left femoral neck | 0.695 | −1.3 |
| Left total hip | 0.712 | −1.2 |
| Lumbar vertebrae | 0.645 | −1.8 |
FRAX scores (10-year probability of sustaining a fracture):
Hip fracture risk: 0.5%
Other major fractures risk: 6.6%
National Osteoporosis Foundation threshold for initiating pharmacologic treatment: Not reached
Vertebral Fracture Assessment: Not done
Has not experienced repeated falls and/or dizzy spells
Multiple choice questions
- 1.
In this patient, risk factors for osteoporosis and low bone mass include:
- A.
Female gender, Caucasian ethnicity.
- B.
Age: 52 years.
- C.
Status postnatural menopause, no hormonal replacement history.
- D.
Positive family history for osteoporosis.
- E.
All of the above.
Correct answer: E
Comments:
All of the above are risk factors for low bone mass and osteoporosis.
- A.
- 2.
In this patient’s case, the following is/are correct:
- A.
The densitometric diagnosis is osteopenia.
- B.
The main goal of management is to maintain and if possible, increase bone mass.
- C.
The fall risk should be thoroughly assessed.
- D.
She should be prescribed an antiresorptive medication to increase the bone mass.
- E.
A and B.
Correct answer: E
Comment:
AC has densitometric evidence of osteopenia: the lowest T-score is less than −1.0, but higher than −2.5. The densitometric difference between osteopenia and osteoporosis is only the extent of mineralization (bone mineral density—BMD), as determined by DXA scans.
This patient had only one DXA scan done. At this stage, therefore, it is not possible to determine whether her skeleton is undergoing bone demineralization or has never reached her maximum potential bone mass. Notwithstanding, the BMD, at the time of examination, is below the normal range. The bones are therefore more fragile than those of a normal reference population and the patient’s fracture risk is therefore increased, although not sufficiently increased to the extent of needing specific pharmacological therapy for osteoporosis.
The patient’s 10-year probability of sustaining a fracture (0.5% and 6.6%, for a hip or major fracture, respectively, as determined by the FRAX scores) is well below the threshold recommended by the National Osteoporosis Foundation to initiate pharmacologic treatment (3% for the risk hip fracture and 20% for other major osteoporotic fractures).
Consequently, if this patient were prescribed medication for osteoporosis, the potential harm, in terms of adverse effects, is higher than the expected benefit associated with a reduction in risk of fractures. The goal of managing this patient therefore is to maintain, and possibly increase the bone mass by nonpharmacological means in order to prevent osteoporosis from developing.
There is no need to pursue the risk of falling as the patient has not sustained any falls and has not experienced any near-falls or dizzy spells. She appears to be physically fit and is leading an essentially healthy lifestyle. Common causes of secondary bone loss have been excluded when she had her annual physical examination. At this stage, therefore, there is no need for any further investigation. However, in about 2 years’ time, she should be evaluated to reassess the state of her bone health and determine whether there has been any bone loss or gain.
- A.
- 3.
The following investigations are recommended:
- A.
Serum CTx (carboxyterminal collagen cross-links).
- B.
Serum P1NP (Procollagen Type I Intact N-terminal Propeptide).
- C.
Bone-specific serum alkaline phosphatase isoenzyme.
- D.
All of the above.
- E.
None of the above.
Correct answer: E
Comment:
C-Tx is a marker of bone resorption. P1NP and bone-specific alkaline phosphatase are markers of bone formation. There is no need, at this stage, for any of the listed laboratory tests. As AC reached the menopause about 2 years ago, she is probably going through the phase of accelerated bone resorption, and therefore if a medication were needed for her bone mass, it would be an antiresorptive medication. If, on the other hand, AC were much older, for instance in her eighties or nineties, she might respond better to an osteoanabolic agent.
- A.
- 4.
At this stage the following investigations are recommended:
- A.
Blood chemistry profile.
- B.
Serum FSH level.
- C.
Serum 25-hydroxy-vitamin D level.
- D.
All of the above.
- E.
None of the above.
Correct answer: E
Comment:
This patient has few reversible risk factors that may predispose to osteoporosis and has taken appropriate actions to prevent it: good daily calcium/vitamin D intake, regular physical exercise, and no cigarette smoking. She also had a number of blood tests, and no pathology has been identified. Given the degree of osteopenia, the clinical condition, the fracture risk, and the results of the blood tests there is no indication, at this stage, for any further tests to be done.
A follow-up DXA scan and evaluation of bone status is nevertheless recommended in about 2 years’ time to monitor her bone status and determine whether she should start on medication to treat osteopenia.
- A.
- 5.
The following is/are recommended:
- A.
Increase daily calcium intake or recommend calcium supplements.
- B.
Recommend vitamin D supplements.
- C.
Increase level of physical activity.
- D.
A and B.
- E.
None of the above.
Correct answer: E
Comments:
AC is already getting an adequate amount of calcium daily through her diet, estimated to be at least 1200 mg (300 mg per 8 oz. of milk or calcium-fortified orange juice) in addition to the dairy products she regularly consumes. There is therefore no need to recommend further increases in the dietary intake or prescribing calcium supplements as this may lead to hypercalciuria and increase the risk of renal calculi.
Her serum vitamin D level is within the normal range (45 ng/mL). There is therefore no need to recommend vitamin D supplements. As she is getting her daily calcium requirements through food, she is, in all probability, also getting enough vitamin D, as evidenced by the normal serum vitamin D level.
She also is already exercising on a regular basis. As far as her bone health is concerned, there is no need to exercise more.
- A.
- 6.
The following therapeutic measures may be considered:
- A.
Starting hormonal replacement therapy.
- B.
Prescribing an antiresorptive medication such as alendronate 35 mg once a week or risedronate 35 mg once a week or 150 mg once a month, ibandronate 150 mg once a month, or zoledronic acid 5 mg once every 2 years.
- C.
Changing estrogen to raloxifene 60 mg once a day.
- D.
A, B, or C.
- E.
None of the above.
Correct answer: E
Comments:
Although all listed alternatives can be useful in this patient, yet, given the degree of osteopenia, the FRAX scores, and the paucity of risk factors for low bone mass and falls, there is no need for any pharmacologic therapy at this stage. The only recommendation is to continue with her healthy lifestyle and repeat the DXA scan in 2 years’ time. The management of her bone health will depend on the change in bone mass over this 2-year period.
Given the adverse effect profile of estrogen and estrogen/progesterone, hormonal replacement therapy is no longer recommended for the management of osteoporosis. It is nevertheless still recommended for the prevention of osteoporosis, provided it is given in the smallest possible dose for the shortest period of time.
- A.
- 7.
The addition of a bisphosphonate to estrogen:
- A.
Induces greater increases in the bone mineral density.
- B.
Interferes with the bioavailability of estrogen.
- C.
Increases the potential for adverse effects.
- D.
Should be avoided as it may oversuppress the rate of bone turnover.
- E.
A and C.
Correct answer: E
Comments:
Bisphosphonates do not interfere with the bioavailability of estrogen. Estrogen, in the USA, is approved for the prevention, but not treatment, of postmenopausal osteoporosis. The Women’s Health Initiative study, a large double-blind, placebo-controlled study confirmed benefits derived from Estrogen (ET) and Estrogen/Progesterone (EPT) therapy. For instance, when compared to placebo, EPT reduced hip fractures by 36%, clinical vertebral fractures by 36%, and other osteoporotic fractures by 23. Similarly, ET reduced hip fractures by 39% and clinical vertebral fractures by 38%.
These trials also confirmed the potential adverse effects of estrogen and progesterone, including thromboembolic disorders, strokes, dementia, endometrial and breast neoplasia. It is, however, possible that in the Women’s Health Initiative study, at least some of these adverse effects were due to the time lag between menopause (i.e., cessation of estrogen production by the ovaries) and initiation of ET and ERT. It has been suggested that if estrogen were administered soon after the onset of the menopause, these adverse effects may have been minimized or prevented.
- A.
- 8.
A repeat DXA scan is recommended in:
- A.
One year.
- B.
Two years.
- C.
Five years.
- D.
When she becomes 65 years old.
- E.
There is no need to repeat the DXA scan.
Correct answer: B
Comment:
One year is too short a period to note any significant change in the BMD as assessed by DXA, especially as the absolute values are so close to the normal range. Five years is too long as her bones may become more demineralized. Two years is a reasonable time. If at that time the BMD has increased, then there will be no need for any pharmacologic agent to be prescribed. If there has been a decrease in bone mass/density, attempts should be made to identify causes of secondary osteoporosis, and if none is identified, specific medication for osteoporosis may be considered. If the bone mass has remained the same, the patient should be encouraged to maintain her lifestyle and another DXA scan will be offered 2 years later.
- A.
- 9.
The following imaging techniques can be used to follow-up patients treated for osteopenia:
- A.
CT scans.
- B.
MRI.
- C.
Ultrasound.
- D.
Plain X-rays.
- E.
None of the above.
Correct answer: E
Comments:
The follow-up imaging of patients treated for osteopenia should be preferably done on the same densitometer, and the precision and accuracy of the DXA scan should be known to ensure that the precision and accuracy of the baseline and follow-up scans are comparable. The least significant change should also be known for the center where scan is done and the technologist performing the scan. These are further discussed in other sections.
- A.
- 10.
The following may be useful additions to consider:
- A.
Testosterone.
- B.
Calcitonin.
- C.
Teriparatide (Forteo) or abaloparatide (Tymlos).
- D.
All of the above.
- E.
None of the above.
Correct answer: E
Comment:
This patient has osteopenia and not osteoporosis. Although the addition of testosterone is also likely to increase the muscle mass, there is a paucity of well-conducted large-scale studies on the effect of adding testosterone to estrogen. Furthermore, testosterone is likely to be associated with a number of adverse effects, including masculinizing effects which most postmenopausal women dislike. The addition of testosterone is therefore not recommended at this stage. Calcitonin has been used for the treatment, not for the prevention of, and for the alleviation of pain postvertebral compression fracture.
Teriparatide and abaloparatide are osteoanabolics approved for the treatment, not prevention of osteoporosis. Furthermore, the cost and the need to administer the medication daily by subcutaneous injections make both medications less likely alternatives for this patient’s management.
- A.
Case summary
Analysis of data
Factors predisposing to bone demineralization/osteoporosis
- •
Status postmenopause.
- •
No hormonal replacement therapy.
- •
Positive family history of osteoporosis, with history of hip fracture in grandmother and kyphosis in mother.
Factors reducing risk of bone demineralization/osteoporosis
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Physically active lifestyle.
- •
Regular exercise sessions.
- •
Good dietary calcium intake.
- •
Moderate alcohol intake.
- •
No coffee, no soda drinks.
- •
No cigarette smoking.
Factors increasing risk of falls/fractures
- •
None.
Factors reducing risk of falls/fractures
- •
Physically active lifestyle.
- •
Regular exercise sessions.
- •
Moderate alcohol intake.
- •
Good dietary intake.
Diagnosis
- •
Osteopenia.
- •
Ten-year fracture risk does not reach threshold recommended by the NOF to initiate pharmacologic treatment.
Management recommendations
Treatment recommendations
- •
No pharmacologic recommendation at this stage.
- •
She is leading a healthy, physically active lifestyle.
Diagnostic test(s)
- •
None indicated at this stage.
Lifestyle
- •
None needed. AC is exercising regularly.
DXA and radiologic
- •
DXA scan in 2 years’ time. Sooner if fractures, falls, or near-falls sustained.
Related posts:
Clinical diagnosis: Fragility fracture long bones
Osteopenia: Individualizing treatment—Part III: When silent vertebral compression fractures override the densitometric diagnosis
Oral bisphosphonates—Lack of response
Zoledronic acid—Annual infusions
Parathyroid hormone analogs
Atypical femoral fractures
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