Learning objectives
- •
Individualizing the management strategy for patients with osteopenia and low fracture risk.
- •
Know when to override the results of the FRAX score and NOF recommendations.
- •
Appreciate the effect of some medications on fracture risk.
- •
Recognize the importance of diet, physical exercise, and lifestyle issues when individualizing the management strategy.
The case study
Reason for seeking medical help
Mrs. GH and her family are concerned because she sustained several falls: about two a week for the past few months. These are usually preceded by bouts of dizziness, especially when she tries to stand up from the seated position or when getting out of bed. She is not aware of any palpitations on standing up. She lives on her own but has good social support.
Past medical/surgical history
- •
Natural menopause at 48 years, no HRT.
- •
Depression, long standing, on sertraline. No suicidal thoughts.
Personal habits
- •
Sedentary lifestyle, especially since she started experiencing bouts of dizziness, near-falls, and falls.
- •
Daily calcium intake about 1200 mg.
- •
At least six cups of coffee and three cans of soda a day, used to consume more.
- •
Smokes about 10 cigarettes a day, used to smoke more. She is planning to stop completely in about 3 months on her birthday.
- •
About three alcoholic drinks daily, binge drinking about once a month.
Medication(s)
- •
Sertraline, 15 years.
- •
Omeprazole, 5 years.
- •
Furosemide, 2 years.
- •
Depo-Provera, 4 years.
Family history
- •
Negative for osteoporosis.
- •
Married, four children, all healthy.
Clinical examination
- •
Weight 185 pounds, height 5′5″, historical height 5′8″.
- •
Mild kyphosis, corrected when asked to stand-up straight.
- •
No relevant clinical findings.
- •
Passive movement of the neck does not induce dizzy spells.
- •
Get-Up-and-Go test completed in 11 s.
Laboratory result(s)
- •
Complete blood count (CBC), comprehensive blood panel (CMP), 25-hydroxy-vitamin D, and thyroid stimulating hormone (TSH) levels done about 4 weeks ago: within normal limits, except for low serum potassium level: 3.1 mmol/L (normal range 3.6–5.2).
DXA and radiological results
| Bone site | T-scores |
|---|---|
| Right femoral neck | −1.6 |
| Right total hip | −1.3 |
| Left femoral neck | −1.5 |
| Left total hip | −1.2 |
| L1-L4 | −2.2 |
- •
FRAX scores (with BMD):
Hip fracture risk: 2.0%
Major fractures: 11%
- •
National Osteoporosis Foundation threshold for initiating pharmacologic treatment: NOT REACHED
- •
Vertebral fracture Assessment: No Vertebral compression fractures
Multiple choice questions
- 1.
In Mrs. GH’s case:
- A.
The densitometric diagnosis is osteopenia.
- B.
The FRAX score does not reach the NOF recommended threshold to initiate pharmacologic treatment for low bone mass.
- C.
The FRAX score should be overlooked because of the patient’s risk of sustaining repeated falls.
- D.
Pharmacologic treatment for low bone mass should be initiated as if the diagnosis were osteoporosis.
- E.
All of the above
Correct answer: E
Comments:
Given that the lowest T-score is −2.2 in the upper four lumbar vertebrae, the densitometric diagnosis is “osteopenia.” As the FRAX scores are 2.7% and 11% for the 10-year risk of sustaining an osteoporotic hip or major fracture, respectively, they do not reach the threshold recommended by the National Osteoporosis Foundation to initiate pharmacologic treatment for osteopenia.
As, however, Mrs. GH has sustained a number of falls, her fracture risk is substantially elevated. She therefore should be offered pharmacologic treatment for osteopenia, as if she had osteoporosis. The cause for her repeated falls also should be addressed and she may benefit from hip protectors.
- A.
- 2.
Depression, Selective Serotonin Reuptake Inhibitors (SSRIs), and bone mass:
- A.
Depression is an independent risk factor for low bone mass.
- B.
SSRIs are independent risk factors for low bone mass.
- C.
SSRIs interfere with the skeletal serotonergic system.
- D.
A and B.
- E.
A, B, and C.
Correct answer: E
Comment:
Depression leads to low bone mass through several mechanisms: increased endogenous cortisol production interfering with the hypothalamic-pituitary-adrenal axis resulting in an excessive amount of catecholamines and increased interleukin-6 release; and also by interfering with the release of growth hormone and hypothalamic-pituitary-gonadal axis, resulting in reduced estrogen/testosterone production. SSRIs also interfere with serotonin receptors and transporters in the osteoblasts and osteocytes and are independent risk factors for osteoporosis. Other factors include low food intake/inadequate diet, sedentary lifestyle, and lack of exposure to sunlight, which may lead to vitamin D deficiency, which is sometimes associated with proximal myopathy and an increased risk of falling.
- A.
- 3.
Depo-Provera (medroxyprogesterone acetate—MPA):
- A.
Decreases estrogen production.
- B.
Leads to bone demineralization.
- C.
The associated BMD loss is totally reversible.
- D.
A and B.
- E.
A, B, and C.
Correct answer: D
Comment:
By decreasing the serum estrogen levels, MPA induces bone demineralization. The greatest loss is observed during the first 2 years of MPA administration. The BMD loss is not totally reversible.
- A.
- 4.
Proton-pump inhibitors (PPIs) increase the risk of:
- A.
Bone demineralization.
- B.
Vertebral fractures.
- C.
Fragility fractures.
- D.
A and B.
- E.
A, B, and C.
Correct answer: E
Comment:
Studies, including at least one prospective study, have shown that PPIs increase the risk of bone demineralization and fragility fractures, including hip fractures. Other studies yielded conflicting results. PPIs decrease calcium absorption, leading to a negative calcium balance, increased parathyroid output, increased bone resorption and bone demineralization, especially if the patient relies on calcium carbonate supplements, which need to be dissolved prior to being absorbed. The dissolution of calcium carbonate requires an acidic medium. The iatrogenic acid suppression also may lead to hypergastrinemia and parathyroid hyperplasia. PPIs also may inhibit osteoclastic proton pumps.
- A.
- 5.
The following is/are true about alcohol consumption:
- A.
Fewer than two units a day do not affect fracture risk.
- B.
Two units a day reduce fracture risk.
- C.
More than two units a day increase fracture risk.
- D.
A and C.
- E.
B and C.
Correct answer: D
Comments:
A study on 5939 men and 11,032 women showed that in both sexes, alcohol consumption exceeding 2 units a day increased the risk of hip fractures (RR 1.68; 95% CI 1.19–2.36), osteoporotic fractures (RR 1.38; 95% CI 1.16–1.65), and any fracture (RR 1.23; 95% CI 1.06–1.43). Alcohol exerts a direct effect on bone cells and modulates factors controlling their activity. Magnesium deficiency may contribute to low bone mass in chronic alcoholism. The “protective” effects of moderate alcohol consumption reported in some observational studies could not be reproduced in controlled studies on experimental animals, suggesting that other factors such as lifestyle changes, including adequate nutritional intake, physically active lifestyle, and avoidance of cigarette smoking, may play a significant role in “protecting” the skeleton.
- A.
- 6.
Cigarette smoking:
- A.
Increases vertebral fracture risk.
- B.
Increases hip fracture risk.
- C.
Its negative effect on bone mass is quickly reversed by discontinuing smoking.
- D.
A and B.
- E.
A, B, and C.
Correct answer: D
Comments:
Cigarette smoking is associated with a smaller bone mass and increased fracture risk. A meta-analysis of 86 studies which included 40,753 subjects showed that cigarette smoking increases vertebral fractures by 13% and 32% in women and men, respectively, and hip fracture risk by 31% and 40% in women and men, respectively. The detrimental effects of cigarette smoking are only partly reversed by smoking cessation.
- A.
- 7.
Sodium intake and calcium metabolism:
- A.
Excess sodium intake leads to hypercalciuria.
- B.
Increasing calcium intake offsets the negative impact of excessive sodium intake.
- C.
Potassium reduces the sodium-induced hypercalciuria.
- D.
A and B.
- E.
A, B, and C.
Correct answer: E
Comments:
Excessive sodium intake induces hypercalciuria through volume expansion and as a result of competition between sodium and calcium ions for the same reabsorption mechanism in renal tubules. In most instances, especially in premenopausal women, hypercalciuria does not lead to a negative calcium balance because of the compensatory increased intestinal calcium absorption.
Postmenopausal women, however, may not be able to sufficiently increase intestinal calcium absorption and therefore the hypercalciuria may lead to a negative calcium balance resulting in increased parathyroid hormone release and increased bone resorption. This increased bone turnover can be offset by increasing daily calcium intake. Potassium also reduces the sodium-induced hypercalcemia . Processed foods are rich in sodium that is difficult to quantify. Salt substitutes are better than salt because potassium reduces the sodium-induced hypercalciuria.
- A.
- 8.
The calciuric effect of carbonated beverages is due to their:
- A.
Caffeine content.
- B.
Sodium content.
- C.
Phosphoric acid content.
- D.
A and B.
- E.
A, B, and C.
Correct answer: D
Comments:
Caffeine increases the renal calcium loss: each 6 oz of caffeine-containing drinks induces a renal calcium loss of 4–6 mg, and the nighttime conservation of calcium is insufficient to offset the excess renal calcium loss. Caffeine also has direct deleterious effects on osteoblast function and survival. Intakes of more than 18 oz of brewed coffee accelerate bone loss in the lumbar vertebrae in postmenopausal women.
Sodium, not phosphoric acid, in carbonated drinks also increases urinary calcium excretion. Phosphoric acid binds to calcium in the gastrointestinal track and reduces its bioavailability and absorption. Notwithstanding, it is probably not the carbonated drink, per se, that increases the risk of bone loss but the fact that it replaces the intake of calcium-containing drinks.
- A.
- 9.
Match the following:
- (a)
Loop diuretics.
- (b)
Hydrochlorothiazides.
- (c)
Both.
- (d)
Neither.
- A.
Increase renal calcium excretion.
- B.
Decrease renal calcium excretion.
- C.
Increase renal potassium loss.
- D.
May lead to urinary incontinence.
- E.
May induce negative calcium balance and bone demineralization.
- A.
Correct answers: A (a); B (b); C (c); D (c); E (a)
Comment:
Loop diuretics increase renal calcium excretion by interfering with its reabsorption at the loop of Henle. Their long-term use may induce a negative calcium balance and bone demineralization. The intake of loop diuretics may lead to hypovolemia which may in turn lead to postural hypotension and bouts of dizziness on standing up or getting out of bed. Thiazide diuretics conserve calcium by increasing calcium absorption at the distal renal tubules thus reducing calcium loss. Loop diuretics and hydrochlorothiazide increase renal potassium loss. All diuretics, particularly loop diuretics, may induce urinary incontinence.
- (a)
- 10.
The following statement(s) is/are true concerning physical exercise:
- A.
In postmenopausal women, walking increases BMD at the lumbar vertebrae and femoral necks.
- B.
In postmenopausal women, walking significantly increases the BMD at the lumbar vertebrae but not femoral necks.
- C.
In postmenopausal women, walking increases the BMD at the femoral necks but not lumbar vertebrae.
- D.
In premenopausal women, high-intensity progressive resistance training increases BMD at the femoral neck and lumbar vertebrae.
- E.
In premenopausal women, high-intensity progressive resistance training increases BMD at the femoral necks but not lumbar vertebrae.
Correct answer: C
Comment:
Exercise studies are notoriously difficult to design, conduct, analyze, and interpret given the complexity of the issue and the numerous factors that modulate the response of the skeleton to physical exercise. Notwithstanding, 2 meta-analyses concluded that in postmenopausal women walking increases the BMD at the femoral necks but not lumbar vertebrae, and in premenopausal women high-intensity resistance training increases BMD at the lumbar vertebrae but not femoral necks.
- A.
Case summary
Analysis of data
Factors predisposing to bone demineralization/osteoporosis
- •
Status postmenopause, no HRT.
- •
Depo-Provera.
- •
Sedentary lifestyle.
- •
Excessive caffeine and sodium intake.
- •
Cigarette smoking.
- •
Alcohol abuse.
- •
Depression and antidepressants (SSRI—Sertraline).
- •
Proton-Pump Inhibitors (Omeprazole).
- •
Loop diuretics (furosemide).
Factors reducing risk of bone demineralization/osteoporosis
- •
Negative family history for osteoporosis.
- •
Good daily calcium intake.
- •
Normal serum vitamin D level.
Factors increasing risk of falls/fractures
- •
Several falls and near-falls sustained.
Factors reducing risk of falls/fractures
- •
Get-Up-and-Go test completed in less than 14 s.
Diagnosis
- •
Osteopenia.
Management recommendations
- •
Given the multiple falls/near-falls experienced by Mrs. GH, her risk of sustaining fractures is increased. Repeated falls is a major factor predisposing to fractures, a risk which is not included in the FRAX permutation. Therefore, even though Mrs. GH has only evidence of osteopenia, not osteoporosis, and even though the fracture risk does not reach the threshold recommended by the National Osteoporosis Foundation to initiate treatment, yet pharmacologic treatment is recommended, especially as Mrs. GH has evidence of a low BMD. Other factors increasing the risk of falls should also be incorporated in the management strategy, including the intake of diuretics which may lead to hypovolemia and orthostatic hypotension. Hypokalemia also may lead to dizzy spells.
Treatment(s)
- •
Pharmacologic management of low bone mass.
Diagnostic tests
- •
No further tests are recommended at this stage.
Lifestyle
- •
In addition to pharmacologic management of low bone mass, nonpharmacologic management and lifestyle changes should be emphasized.
DXA and radiologic
- •
Repeat DXA scan in 2 years to monitor BMD and fine-tune the management strategy.
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