Learning objectives
- •
Osteoporosis is also common in very old age. It is often underrecognized, underdiagnosed, and undertreated.
- •
Osteoporosis is less frequent in older men than in women, but its mortality and morbidity are worse.
- •
As with younger patients, for best results, a comprehensive approach is recommended: the pharmacologic management should be complemented by lifestyle changes and an adequate diet.
The case study
Reason for seeking medical help
- •
Mr. WM, 89 years old, is concerned he may have osteoporosis: about 2 weeks ago, while on a Mediterranean cruise, he tripped over a cable, slipped, fell, and sustained only superficial, albeit extensive bruises. A medical doctor among the passengers noticed the episode and recommended a medical examination. He is essentially asymptomatic. In about a month’s time he is scheduled to go on a four-week “total immersion” tour in South Africa. He has been warned that this tour is quite demanding physically and mentally. He was offered the option to withdraw, but he is very keen to go on this adventure tour: “A once in a lifetime experience.”
Past medical/surgical history
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Hyperlipidemia, well controlled.
Personal habits, lifestyle, daily routine
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Mr. WM is a widower, has no children, and no close relative alive. He lives on his own; is asymptomatic; cognitively intact; physically independent; drives his own car; travels extensively; and denies dizzy spells, falls, and near-falls. He has no hobby except reading and traveling.
- •
He is a retired college teacher and continues to be involved teaching Medieval History. He has written three books and is often invited to give talks to academic circles and the lay public.
- •
When not traveling, he leads a sedentary lifestyle.
- •
Average daily caffeine intake: 4 cups, about 16 oz each cup.
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Daily calcium intake: average 1000 mg.
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Alcohol intake: about two drinks most days, occasionally more when he is with friends.
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Cigarette smoking: about 10 cigarettes a day, used to smoke more. He is planning to stop smoking.
- •
Enjoys chocolates and salty food.
Medications
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Simvastatin 40 mg daily for “many years.”
- •
Aspirin, 81 mg, once a day, also, for “many years.”
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Multivitamin tablets once a day.
- •
Over-the-counter sleep aids, on an as-needed basis, not exceeding one tablet a week.
Family history
- •
Negative for osteoporosis.
Clinical examination
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Weight 186 pounds, steady, height 62.75″, used to be 66.5″, arm span 65.5″.
- •
Mild kyphosis, that, to a large extent, can be corrected by changing posture.
- •
No clinical signs suggesting an increased fracture risk:
- ○
Sitting BP 136/85, standing BP 142/86, no orthostasis.
- ○
No clinical evidence of carotid stenosis, carotid sinus sensitivity, and vertebrobasilar insufficiency.
- ○
No localizing neurological signs, cerebellar functions intact.
- ○
No clinical evidence of fluid retention, edema of the lower limbs, or heart failure. No evidence of pulmonary congestion. Lungs clear.
- ○
Laboratory investigations
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Comprehensive metabolic profile: no abnormal finding.
- •
Serum 25-hydroxy-vitamin D: 42 ng/mL.
DXA scan results
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T-scores: right femoral neck: −2.1, right total hip: −1.5, distal 1/3 radius: −1.3; L1–L4: cannot be reliably interpreted because of osteophytes. Left hip was not scanned.
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Vertebral fracture assessment: no evidence of vertebral compression fractures.
- •
FRAX score (with BMD): hip fracture: 3.7%; other major osteoporotic fractures: 22%.
Multiple choice questions
- 1.
In Mr. VM’s case, the final diagnosis is:
- A.
Densitometric diagnosis: osteoporosis.
- B.
Densitometric diagnosis: osteopenia.
- C.
Fracture risk exceeds NOF threshold to initiate therapy.
- D.
B and C.
- E.
A and C.
Correct answer: D
Comment:
The densitometric diagnosis is osteopenia. It is nevertheless overridden by the fracture risk, as per the FRAX score, exceeding the threshold recommended by the National Osteoporosis Foundation Guidelines to initiate pharmacological therapy: 20% and 3% for the risk of major and hip fracture, respectively.
Therefore, unless there are contraindications, this patient should be treated as if he had osteoporosis, including medications, reducing alcohol and caffeine intake, discontinuing cigarette smoking, and discontinuing the intake of hypnotics, especially those obtained over the counter as their half-lives are often long and may induce daytime sleepiness, disequilibrium, repeated falls and fractures.
Other recommendations include adopting a physically active lifestyle and especially a combination of resistive and aerobic exercises. Several programs are now available in many public gymnasia. Old age should not be a hindrance to enroll in these programs.
- A.
- 2.
The following laboratory tests are recommended:
- A.
Fasting serum C-TX.
- B.
Fasting serum P1NP or alkaline phosphatase bony isoenzyme.
- C.
Ionized serum calcium level.
- D.
All of the above.
- E.
A and B.
Correct answer: E
Comment:
Bone markers are available to estimate the rate of bone formation and bone resorption. They therefore differentiate patients who may benefit from medication that stimulates bone formation (osteoanabolics) from those who would benefit from medication that reduces the rate of bone resorption (antiresorptives).
The fasting serum carboxy-terminal collagen cross-link (Crosslaps, C-TX, serum cross-linked C-telopeptide of type 1 collagen) is a marker of bone resorption. The fasting serum Procollagen Type I intact N-terminal Propeptide (P1NP) and alkaline phosphatase bony isoenzyme are markers of bone formation.
Ideally therefore one should assay bone markers to select, fine tune, and monitor the management strategy. Patients whose rate of bone resorption is elevated, or are at the upper end of normality, are more likely to benefit from an antiresorptive and those with a reduced or at the lower end of normality are likely to benefit from an osteoanabolic medication.
A question that sometimes arises is whether it is appropriate to initiate pharmacological treatment in very old patients found to have an increased fracture risk. Given the potential impact of any fracture, especially hip fractures on morbidity and mortality, the answer should be a resounding YES! The impact of a hip fracture on patients similar to Mr. WM is such that quality of life and loss of autonomy with activities of daily living are likely to be severely affected. A study conducted in Europe shows that overall mortality in men, within 1 year of a hip fracture, increases from 15% before the age of 65 years to more than 30% after the age of 75 years. In women, one-year mortality rate is less than 10% before the age of 70 years but increases to 30% after the age of 90 years.
- A.
- 3.
The following medication(s) are most helpful at this stage:
- A.
Antiresorptives.
- B.
Osteoanabolics.
- C.
Vitamin supplementation.
- D.
A and C.
- E.
B and C.
Correct answer: B
Comment:
The skeletal mass goes through three distinct phases. First, a phase of bone accretion during childhood and adolescence. During this period the rate of bone formation exceeds the rate of bone resorption and the bone mass increases relatively quickly. During the second phase, the phase of consolidation, the rate of bone formation and bone resorption are about the same, the skeleton stops growing, but is continuously remodeled: old bone is resorbed and new bone, better able to meet various physical stressors, is formed. The bones get denser.
This is followed by the third phase when bone resorption exceeds bone formation and the skeletal mass decreases. In women this phase starts rather abruptly with the cessation of menstruation. The skeleton of men too goes through these phases albeit about a decade later than women.
Given the patient’s age, 94 years, it is very likely that bone loss exceeds bone formation. An osteoanabolic agent therefore is likely to be more efficacious than an antiresorptive. Finally, given that skeletal mass tends to respond better when it is first stimulated by the osteoanabolics and then resorption is inhibited, rather than being inhibited first by antiresorptives and then attempts made to stimulate bone formation. Notwithstanding, a medication that can be parenterally administered should be recommended to ensure the patient takes it as recommended. At present, several medications for osteoporosis can be parenterally administered and include: zoledronic acid intravenous infusion, once a year; denosumab, one injection subcutaneously every 6 months; and romosozumab, subcutaneous injection every month.
- A.
- 4.
The incidence of fragility fractures:
- A.
Most fragility fractures occur before the age of 50 years.
- B.
About half of the fractures occur after the age of 75 years.
- C.
Affects about 20% of women aged 60 years.
- D.
Affects about 50% of women aged 80 years.
- E.
All of the above.
Correct answer: B
Comment:
Osteoporosis in old age continues to be underdiagnosed and undertreated especially in older people. And yet, the threshold between undertreatment and overtreatment is unclear especially in patients with limited life expectancy.
Concerning fragility fractures :
- •
Few fragility fractures occur before the age of 50 years.
- •
About half of the fractures occur after the age of 75 years.
- •
About 10% of women 60 years old sustain fractures.
- •
About 20% of women aged 70 years old sustain fractures.
- •
About 40% of women aged 80 years old sustain fractures.
- •
Two-thirds of women aged 90 years and older sustain fractures.
Similarly, a review of 377,561 female Medicare beneficiaries who sustained a fracture reveals that 10%, 18%, and 31% sustained another fracture within 12 months, 24 months, and 60 months of the original fracture, respectively. Finally, a real-world cohort over the age of 65 years revealed that, regardless of the site of fragility fractures, mortality is increased for up to 6 years postfracture.
- A.
- 5.
Factors increasing the risk of fragility fractures:
- A.
Older age.
- B.
Lower body weight.
- C.
Greater height loss when compared to height at age 25 years.
- D.
Hyperthyroidism.
- E.
All of the above.
Correct answer: E
Comment:
All the previously mentioned increase the risk of falls and fractures as per the Osteoporotic Fractures in Men Study. A prospective study on 5994 men, primarily White, 65 years of age or older, recruited at six US clinical centers. During a mean of 8.6 years, 97% completed follow-up, 178 men sustained a hip fracture. Other findings of this study include :
- •
Almost 30% of hip fractures occur in older men.
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Mortality, morbidity, and loss of independence after a hip fracture are greater in men than in women.
- •
Although assessment protocols are available to identify patients likely to sustain an initial or first fragility fracture, scarce information is available about predicting the sequelae of second and subsequent fractures.
- A.
- 6.
Osteosarcopenia:
- A.
Is a benign, age-associated, loss of skeletal and muscle mass.
- B.
Affects about 70% of adults aged 70 years or more.
- C.
Increases the fracture risk.
- D.
B and C.
- E.
A, B, and C.
Correct answer: C
Comment:
Osteosarcopenia is characterized by the simultaneous loss of muscle and bone density, culminating in functional decline, physical disability, increased falls and fracture risk, and poor quality of life. It is estimated to affect more than 40% of patients aged 70 years or older.
- A.
- 7.
Factors affecting ability to conduct activities of daily living after a hip fracture include:
- A.
Age.
- B.
Depression.
- C.
Prefracture ability to conduct activities of daily living.
- D.
Nutritional status.
- E.
All of the above.
Correct answer: E
Comment:
All listed factors affect functional recovery outcome after sustaining a hip fracture.
If the patient is to be discharged back home, an evaluation of the home/institution conditions would help ensuring the patient is safe and able to cope with activities of daily living, including the intake of medications. Often older people find it difficult to open the tablet containers and may not be able to read the directions as to when to take the medication.
The need for long-term care following a hip fracture increases significantly with age from 4% in those aged 70–79 years, to 14% for those aged 80–89 years, and 35.3% in those between the ages of 90 and 100 years.
Hip fractures are life-changing events, hence the urgency of treating patients who are at high risk of sustaining a hip fracture. Similarly, as soon as possible after the surgery is completed, these patients should be thoroughly evaluated and enrolled in a rehabilitation program tailored to the individual deficits and needs of the patient.
- A.
- 8.
Factors increasing the risk of falls and fractures include:
- A.
Age.
- B.
Comorbidities.
- C.
Decreased mental alertness.
- D.
Balance and gait abnormalities.
- E.
All of the above.
Correct answer: E
Comment:
All listed factors affect functional recovery outcome after sustaining a hip fracture. Other factors include low femoral neck BMD, current smoking, greater height, height loss since age 25 years, use of tricyclic antidepressants, history of myocardial infarction, hyperthyroidism, Parkinson’s disease, and low protein intake.
- A.
- 9.
The initial evaluation of older men after a fracture is sustained should include:
- A.
An assessment of the clinical impact of the disease.
- B.
An evaluation of the patient’s cognitive functions.
- C.
An evaluation of the risks of falling.
- D.
The presence of comorbidities.
- E.
All of the above.
Correct answer: E
Comment:
An initial systematic thorough evaluation is necessary once the diagnosis of osteoporosis is established. This should include the potential impact on the risk of falling and fractures, as well as the ability to live in the prefall/prefracture environment.
An assessment of cognitive functions is also important to determine whether the patient is able to make medical and financial decisions. An often overlooked issue is whether the patient is mentally and physically capable to self-administer prescribed medication. The home environment also should be assessed, including the patient’s safety and ability to call for help.
- A.
- 10.
Frailty:
- A.
Has definite, clear-cut parameters to establish a diagnosis.
- B.
Is responsible for negative health events.
- C.
Is more common among individuals who have sustained a fracture.
- D.
B and C.
- E.
A, B, and C.
Correct answer: D
Comment:
Frailty is considered to be a state of vulnerability and poor adaptability to pathological, psychological, social, or pharmacological assaults. It is responsible for negative health events, including disability, institutionalization, and death. It could be an effective predictor of osteoporotic fracture, but unfortunately lacks a clear definition and quantification.
Other factors increasing the risk of subsequent hip fracture include older age, male sex, degree of autonomy, femoral neck and total hip bone mineral density. Several diseases increase the risk of fracture after a hip fracture, including neurological diseases, chronic obstructive pulmonary disease, diabetes mellitus, and heart failure.
- A.
Case summary
Analysis of data
Factors predisposing to bone demineralization/osteoporosis in WM’s case
- •
Sedentary lifestyle, when not traveling.
- •
Living on his own since his wife died. In this cohort, the risk of malnutrition is increased and may lead to loss of bone and muscle bulk, weakness, unsteadiness, and increased falls and fractures risk.
- •
Cigarette smoking.
- •
Alcohol intake.
Factors reducing the risk of bone demineralization/osteoporosis
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The physical exercises undertaken while traveling.
- •
Intact cognition.
Factors increasing the risk of falls/fractures
- •
Alcohol intake.
- •
Living alone.
Factors reducing the risk of falls/fractures
- •
Active lifestyle.
Bone health diagnosis
- 1.
Densitometric diagnosis:
Osteopenia, as manifested by the lowest T-score (−2.1) of the right total hip, right femoral neck, right total hip, or distal radius. The lumbar vertebrae BMD could not be appropriately analyzed because of the presence of osteophytes and osteoarthritic changes.
- 2.
Increased fracture risk:
According to the Fracture Risk Assessment algorithm (FRAX Score), the 10-year probability of sustaining a fracture is 3.7% and 22% for the risk of a hip and major fracture. These probabilities exceed the threshold recommended by the National Osteoporosis Foundation to initiate pharmacological treatment to reduce the fracture risk.
The final diagnosis therefore is osteopenia, with fracture risk exceeding the NOF threshold to initiate pharmacologic treatment.
Management recommendations
Further diagnostic tests
Markers of bone resorption and bone formation to determine whether an antiresorptive or an osteoanabolic should be the first medication to be offered. The results of these tests will also determine whether the prescribed medication is the most efficacious in this particular patient at this point in time and can be used to monitor the patient’s response to the prescribed medication.
Treatment recommendations
Medications
- •
Osteoanabolic agent.
Physical therapy/lifestyle changes
Ideally the patient should be enrolled in an exercise program supervised by an experienced physical therapist/occupational therapist and tailored to the specific needs of the individual patient. The goal is for the patient to reach confident independence to perform all the needed Activities of Daily Living (ADL).
Follow-up
A visit or telehealth encounter 4–6 weeks after starting therapy is appropriate to ensure the patient is taking the medication as directed and has not encountered any difficulty. This visit also emphasizes the importance of osteoporosis and its pharmacological treatment as well as the prescribed lifestyle changes.
Further follow-up visits will depend on the patient’ condition and circumstances.
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