Learning objectives
- •
A fragility fracture, per se, is diagnostic of osteoporosis and increases the risk of further fractures.
- •
The impact of hazardous environments leading to falls and fractures.
- •
The integration of medical history, clinical findings, densitometric results, FRAX results, and NOF recommendations to develop a management plan tailored to individual patients.
The case study
Reason for seeking medical help
- •
MG is a 57-year-old Caucasian woman. Her daughter is concerned she may have osteoporosis because about 6 months ago she sustained a fracture of the right distal radius after tripping over a small rug in her bedroom, falling onto the bed and then sliding onto the floor. She recovered very well, resuming full function of her right wrist and hand. She was given an appointment at the bone clinic but did not go because she did not feel there was anything wrong with her bones, especially as she recovered so well after the fracture. She feels very well, has not lost any height, and leads a socially active lifestyle. She is essentially asymptomatic.
Past medical and surgical history
- •
Right Colles’ fracture about 6 months ago, excellent recovery.
- •
She has not sustained any fall and did not experience “near-falls.”
- •
Natural menopause at age 51 years, no hormonal replacement therapy.
- •
Menarche at age 12 years, regular menstrual periods.
- •
Three children aged 36, 33, and 30 years, all in good health.
Lifestyle
- •
Independent, lives with her husband, and drives her own car. Both enjoy traveling.
- •
Sedentary lifestyle, except for swimming for about an hour, three to four times a week.
- •
Works as a receptionist in a dentist’s office.
- •
Good appetite, healthy, well-balanced diet.
- •
Daily calcium intake from food estimated to be about 1200 mg.
- •
No cigarette smoking, no recreational drugs, no caffeine, no soft drinks, low sodium intake.
- •
Occasional glass of wine with dinner, once or twice a week.
Medication(s)
- •
No medication prescribed or over the counter.
Family history
- •
Negative for osteoporosis.
- •
Mother and father alive and well.
Clinical examination
- •
Weight 135 pounds, height 65″ no kyphosis.
- •
Vision good, has bifocal eyeglasses.
- •
Hearing good; no hearing aids.
- •
Lying BP 125/82; standing BP 128/81, no orthostasis.
- •
No clinical evidence of carotid sinus sensitivity, carotid stenosis, or vertebrobasilar insufficiency. Passive movement of the neck does not induce any pain that may suggest cervical spondylosis.
- •
Gums healthy. She visits her dentist every 6 months.
- •
No other significant clinical findings.
- •
Get-up-and-Go test completed in 5 s.
Laboratory result(s)
About 2 weeks before her visit she had a number of laboratory tests done as part of her annual examination. All results were within normal limits, including complete blood count (CBC), comprehensive metabolic panel (CMP), serum vitamin D, parathyroid hormone (PTH), and thyroid stimulating hormone (TSH).
DXA and radiological result(s)
- •
Lowest T-score −1.8 in the upper four lumbar vertebrae.
- •
Vertebral fracture assessment: no evidence of vertebral compression fracture.
- •
FRAX scores (MG’s probability of sustaining a hip or major fracture in the next 10 years): 1.2% for the risk of hip fracture and 12% for the risk of a major fracture, respectively. These thresholds do not reach the level recommended by the National Osteoporosis Foundation to initiate treatment to increase BMD and reduce the risk of fractures.
Multiple choice questions
- 1.
In MG’s case, factors increasing the risk of low bone mass and osteoporosis include:
- A.
Status postmenopause.
- B.
No hormonal replacement therapy.
- C.
Sedentary lifestyle.
- D.
Caucasian ethnicity.
- E.
All of the above.
Correct answer: E
Comment:
All the listed factors increase the risk of low bone mass and osteoporosis. Fragility fractures of the distal radius occur much earlier than fractures of the hip and are often due to underlying abnormalities of bone mass and bone architecture. They offer a unique and ideal opportunity to evaluate, diagnose, and treat fragile bones and reduce the risk of subsequent fractures.
- A.
- 2.
In MG’s case, factors reducing the risk of osteoporosis include:
- A.
The regular swimming exercises she undertakes.
- B.
A negative family history for osteoporosis.
- C.
No cigarette smoking.
- D.
Low sodium and caffeine intake.
- E.
B, C, and D.
Correct answer: E
Comment:
Unlike most other physical exercises, it is debatable whether swimming has the same protective effects on the skeleton. Cigarette smoking increases the risk of low bone mass and osteoporosis. It is, however, debatable whether this is due to the cigarette smoking per se or whether it is due to the lifestyle many smokers adopt, including sedentary lifestyles and low level or lack of physical activities.
Excessive caffeine and sodium intake induces a negative calcium balance by increasing the renal calcium loss which may trigger the release of parathyroid hormone and stimulate the osteoclasts to increase bone resorption in an attempt to mobilize calcium from the bones to the circulation, thus leading to a low bone mass and possibly osteoporosis. Many soft drinks also contain phosphates which may interfere with the intestinal absorption of calcium.
- A.
- 3.
In MG’s case, factors increasing the risk of falls (and hence fractures) include:
- A.
The fall she sustained 6 months ago that resulted in a fragility fracture of the radius.
- B.
The bifocal glasses she wears.
- C.
Small rug(s) in her bedroom, if still present.
- D.
All of the above.
- E.
None of the above.
Correct answer: D
Comment:
All of the above increase the risk of falls and therefore fractures. The fall she sustained about 6 months ago also increases the risk of sustaining further fractures. Although most fractures are preceded by falls, most falls do not result in fractures. This gives clinicians a unique opportunity to identify patients who are at risk of sustaining falls.
Bifocal eyeglasses are sometimes responsible for repeated falls because the area immediately around the patient’s feet is perceived through the lower lenses which are meant to be used for near vision, such as reading. As a result, while wearing bifocal glasses the patient may misjudge the proximity and size of obstacles in her path, may stumble over them and fall. This is particularly likely to happen when the patient is going up or down the stairs. It is safer for older people who need reading glasses to have two sets of eyeglasses: one for distant vision and one for near vision. Similarly, small rugs on the floor should be avoided as they increase the risk of falling.
A sedentary lifestyle also increases the risk of muscle wasting which further increases the risk of falls and therefore fractures.
- A.
- 4.
In MG’s case, factors reducing the risk of falls (and hence fractures) include:
- A.
No history of falls and no near-falls.
- B.
No clinical evidence of vertebrobasilar insufficiency.
- C.
No clinical evidence of carotid stenosis or carotid sinus sensitivity.
- D.
B and C.
- E.
A, B, and C.
Correct answer: E
Comment:
About 6 months ago, MG sustained a fall that led to a fragility fracture. A number of pathologies may increase the risk of falling including carotid stenosis, a sensitive carotid sinus, vertebrobasilar insufficiency, and any pathology increasing the risk of light-headedness, dizziness, unsteadiness, and falls. Clinically carotid stenosis is suspected when the pulsations of one carotid artery are weaker than those of the contralateral side. Auscultation may reveal the presence of an ejection systolic murmur.
Vertebrobasilar insufficiency often presents with bouts of dizziness that may be clinically reproduced by passively moving the patient’s head. It is often due to cervical spondylosis which causes the cervical vertebrae to become malaligned with the potential of interfering with the cerebral blood flow as the vertebral artery cruises inside the transverse process of the cervical vertebrae before joining the contralateral artery to form the basilar artery which perfuses the cerebellum where posture, equilibrium, and balance are coordinated. A sensitive carotid sinus should be considered if the patient’s heart rate slows, or stops, when gentle pressure is applied on the carotid sinus. MG has none of the previously mentioned symptoms.
- A.
- 5.
In MG’s case:
- A.
The FRAX scores reach the threshold recommended by the NOF to initiate pharmacologic treatment.
- B.
The clinical diagnosis of osteoporosis (based on the patient sustaining a fragility fracture) overrides the densitometric diagnosis.
- C.
She should be offered pharmacologic treatment for osteoporosis.
- D.
The NOF guidelines are overridden by the presence of a fragility fracture.
- E.
B, C, and D.
Correct answer: E
Comment:
The FRAX scores (1.2% and 12% for the 10-year probability of sustaining a hip or major fracture, respectively) do not reach the threshold recommended by the National Osteoporosis Foundation to initiate pharmacologic treatment (3% and 20% for the probability of sustaining a hip or major fracture, respectively).
The presence of fragility fractures, however, overrides the T-scores, FRAX scores, and NOF recommendations as these fractures are, per se, diagnostic of osteoporosis and warrant pharmacologic treatment after excluding localized bone diseases. In fact, in these patients DXA scans are not needed to make a diagnosis of osteoporosis or osteopenia but, as previously noted, are needed to establish a baseline against which the patient’s progress, or lack of progress, may be noted.
One of the major deficiencies of the FRAX algorithm is that falls are not taken into consideration in the permutation to calculate the fracture risk. In these patients therefore, FRAX scores underestimate the real risk of fractures. Once a fracture is sustained the risk of sustaining further fractures is increased.
- A.
- 6.
The final diagnosis is:
- A.
Osteoporosis.
- B.
Osteopenia.
- C.
Status postfragility fracture of the distal radius.
- D.
A and C.
- E.
B and C.
Correct answer: D
Comment:
The presence of a fragility fracture is, per se, diagnostic of osteoporosis and an indication that pharmacologic treatment, supported by a healthy lifestyle, should be prescribed and individualized for each patient. In these instances, a DXA scan is required not to confirm the diagnosis, but to establish a baseline against which the patient’s progress, or lack of progress, can be assessed.
- A.
- 7.
The following assessments are recommended:
- A.
An assessment of cognitive functions such as the Mini Mental Status Examination (MMSE) or Montreal Cognitive Assessment (MoCA).
- B.
A depression scale.
- C.
A falls risk assessment.
- D.
A comprehensive nutrition evaluation.
- E.
None of the above.
Correct answer: E
Comment:
At this stage there is no indication for any of the listed assessment scales. MG is independent, actively employed, and drives her own car safely. She sustained a single fall which could be attributed to the bifocal eyeglasses she had acquired only a few days before the fall. Since then, she has not experienced any other falls or near-falls. There is therefore no need for any of the previously mentioned assessments to be done at this stage.
- A.
- 8.
Pharmacologic management recommendations include:
- A.
A selective estrogen receptor modulator: raloxifene.
- B.
A bisphosphonate: alendronate, risedronate, ibandronate, or zoledronic acid.
- C.
A RANK-Ligand antagonist: denosumab.
- D.
An osteoanabolic medication: teriparatide, abaloparatide, or romosozumab.
- E.
A, B, or C.
Correct answer: A, B, or C
Comment:
The presence of a fragility fracture is diagnostic of osteoporosis and overrides the densitometric diagnosis. In MG’s case, the fracture of her right wrist is a fragility fracture because it is the result of trauma that ordinarily would not be expected to result in a fracture: she tripped over a rug in her bedroom and fell on the bed and then slid on the carpet.
MG should be treated pharmacologically for osteoporosis as soon as possible, even though the DXA scan shows evidence of only osteopenia, not osteoporosis and even though the FRAX scores do not reach the threshold recommended by the NOF to initiate treatment in patients with osteopenia.
There is some urgency to prescribe a medication to increase the bone mass. Patients who sustain fragility fractures are likely to sustain more fractures. The morbidity and mortality associated with fractures are substantial, even after the fracture itself has healed well.
At this stage, given the age of the patient (57 years), the magnitude of bone loss, as well as the cost of the medication, most clinicians would prescribe first an antiresorptive medication and observe the patients’ response to treatment. A weak or lack of response will trigger a series of tests to identify possible causes of secondary osteoporosis. This issue is discussed in a different case study.
- A.
- 9.
Nonpharmacologic recommended management includes:
- A.
Engage in resistive and aerobic exercises.
- B.
Ensure an adequate daily calcium and vitamin D intake.
- C.
Take calcium and vitamin D supplements.
- D.
A and B.
- E.
A, B, and C.
Correct answer: A
Comment:
A combination of aerobic and resistive exercises has been shown to increase bone mass. Given that MG enjoys water exercises, she may be offered the opportunity of performing resistive exercises while in the pool, such as, for instance, walking in the shallow end of the pool while wearing flippers. Overcoming the resistance to the flippers in the water is a form of resistive exercise. Unfortunately exercise-induced increases in bone mass decrease if the person stops exercising regularly.
Given that MG’s daily dietary calcium and vitamin D intake is within the recommended limits, there is no need for calcium supplementation.
- A.
- 10.
The following follow-up is recommended:
- A.
Repeat DXA scan in 1 year.
- B.
Repeat DXA scan in 2 years.
- C.
Repeat DXA scan in 5 years.
- D.
Repeat the FRAX score in 6 months.
- E.
None of the above.
Correct answer: B
Comment:
Once pharmacologic management is initiated it is useful to repeat the DXA scans to monitor the patient’s response (or lack of response) to treatment. Although patients’ compliance is quite good in clinical trials, in real life, compliance, especially with the intake of oral bisphosphonates, is low and frequently patients do not adhere to the directions on how to take oral bisphosphonates: while fasting, with 6 oz of water and to refrain from eating, taking any medication, and drinking any fluid but water for 30 min (alendronate and risedronate) or 60 min (ibandronate) after taking the medication. Patients need to be motivated. Without reinforcements they may discontinue taking the medication or may not take it exactly as directed. Compliance with denosumab is better than with oral bisphosphonates. This is discussed further in the chapter on denosumab.
Repeating the DXA scan more often than every other year is unlikely to yield significant changes, i.e., changes exceeding the Least Significant Change (LSC) and may actually backfire and encourage discontinuation of the antiresorptive medication if the patient erroneously feels the lack of increase in BMD is due to lack of effect.
On the other hand, a positive change exceeding the LSC will encourage the patient to continue with the medication. A smaller change or a negative change in BMD will alert the treating clinician that the patient may have stopped taking the medication or may have stopped adhering to the prescribed regimen or may have secondary osteoporosis.
It is not recommended to repeat the FRAX score once pharmacologic treatment is initiated because the patient’s age influences so much the fracture risk, as calculated by the FRAX permutation, that any change in BMD/T-score is likely to be obscured by the patient’s age. Similarly, some of the medication-induced changes in trabecular bone thickness may not be captured by DXA scans.
Not being able to monitor the patient’s response to treatment with the FRAX algorithm is a drawback as patients who have been motivated to take their medication based on the FRAX score are no longer able to assess their progress or lack of progress.
- A.
Case summary
Analysis of data
Factors predisposing to bone demineralization/osteoporosis
- •
Status postnatural menopause, no hormonal replacement therapy.
- •
Sedentary lifestyle.
Factors reducing risk of bone demineralization/osteoporosis
- •
Good, well-balanced diet.
- •
No excessive sodium and caffeine intake.
- •
No excessive phosphate intake.
- •
Moderate alcohol intake.
- •
No cigarette smoking.
Factors increasing risk of falls/fractures
- •
Bifocal eyeglasses.
- •
Possible hazardous environment such as small rugs in the bedroom.
Factors reducing risk of falls/fractures
- •
None.
Diagnosis
- •
Osteoporosis, as evidenced by the fragility fracture of the right distal radius.
- •
The presence of a fragility fracture, per se, justifies the diagnosis of osteoporosis and overrides the results of bone densitometry, FRAX scores, and National Osteoporosis Foundation recommendations as to when therapy for osteoporosis should be initiated. The fact that the fracture has healed well suggests MG should respond well to antiresorptive therapy after secondary causes of osteoporosis have been ruled out.
Management recommendations
Medical management
- •
Antiresorptive medication.
- •
Lifestyle changes, including active lifestyle, adequate, well-balanced diet, and physical exercises.
Further diagnostic test(s)
- •
None at this stage. She has been adequately investigated for secondary osteoporosis.
If, however, there is concern the patient may not adhere to the medication prescribed, the changes in blood levels of bone markers before starting the medication and 6 to 8 weeks later would confirm whether she is taking the medication as directed, whether it is absorbed, and whether it is working. Markers of bone resorption, such as serum cross-linked C-telopeptide of type I collagen (CTx), can be assayed if she is prescribed antiresorptive medication. Similarly, markers of bone formation such as Procollagen Type I Intact N-terminal Propeptide (P1NP) or bone-specific alkaline phosphatase isoenzyme can be used to monitor the changes in markers of bone formation, and hence the rates of bone formation. There is no need for any of these tests if the patient is prescribed parenterally administered medication. Biomarkers are discussed separately.
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