Michael Gunawan 030.06.

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 Osteoporosis Skeletal disorder characterized by decrease bone

mass and deterioration of bony microarchitecture.

The result: Fragile bones and risk for fracture. BMD is reduced, bone microarchitecture is disrupted, and the

amount and variety of non-collagenous proteins in bone is altered.

Corticosteroid (CS) therapy: Treatment of rheumatic diseases

Major complications: Osteoporosis.

Preventative treatment for osteoporosis in patients on CS remains

low.

 Pathogenesis

of CIOP differs from postmenopausal

osteoporosis in that bone formation is said to be more suppressed compared with bone resorption.
Diagnosis of CIOP Clinical risk factors and may not

require measurement of BMD.

BACKGROUND
Osteoporosis Skeletal fragility Decreased bone mass

and microarchitectural deterioration of bone tissue Risk of

fracture.
Fracture: Form of cracking (as in a hip fracture), or collapsing

(as in a compression fracture of the vertebrae of the spine).

Spine, hips, and wrists are common areas of osteoporosis-

related bone fractures.

 Patients on CS therapy Risk of sustaining fractures. In patients with RA Incidences of hip, vertebral, and distal

forearm fractures increase.

Problems in CIOP is that in many of the underlying diseases where

CS are used, bone loss may already be present even before CS are started.

PROBLEMS
What is osteoporosis? How can corticosteroid therapy cause osteoporosis? What is management to prevent corticosteroid-induced osteoporosis?

 Osteoporosis is a condition that features loss of the normal

density of bone and fragile bone.

Normal bone: protein, collagen, and calcium. Bones that are affected by osteoporosis can fracture with only

a minor fall or injury.

Spine, hips, and wrists: common areas.

 Etiological factors of primary osteoporosis Family history

of fracture or low bone mass.

Menopause a rapid reduction in BMD Risk fractures of

the wrist, spine and hip.

Hormone deficiency , glucocorticoid or thyroxine, and calcium

and/or vitamin D deficiency Risk of osteoporosis.

Calcium and vitamin D Normal bone growth.

 Imbalance bone resorption and bone formation Bone

resorption is excessive, bone formation is diminished.

Bone matrix: osteoblast cells.
Bone resorption: osteoclast cells. Bone remodeling Nutritional and hormonal factors. Parathyroid hormone Composition of bone. Glucocorticoid hormones Osteoclast. Calcitonin and estrogen Osteoblast .

 Dual energy X-ray absorptiometry (DXA): Gold standard. Diagnosis BMD is less than or equal to 2.5 standard

deviations (T - Score).
WHO: Criteria for the Diagnosis of Osteoporosis (1) CATEGORY
Normal Osteopenia Osteoporosis Severe Osteoporosis CRITERIA (EXPRESSED AS T - SCORE)
Patient BMD 1 SD of average peak young adult BMD (T-score, 0 to -1)

Patient BMD between 1 SD and 2.5 SD below average peak young adult BMD (T-score, -1 to -2.5) Patient BMD 2.5 SD below average peak young adult BMD (T-score, 2.5) Patient BMD 2.5 SD below average peak young adult BMD with fragility fractures

 Fractures: Most frequent and serious complication. Hip fractures: The second most common type

Disability and death.

Spinal fracture Without any fall or injury Vertebrae

become so weakened Compression fractures

Severe pain and long recovery.

Clinical risk factors for osteoporosis(4).

Previous vertebral fracture or low trauma appendicular

fracture Post-menopausal woman not receiving HRT Premature menopause at <45 year or male hypogonadism Age > 65 year Planned or current CS use of > 6 months Low BMI: < 20 kgum2 History of low trauma maternal hip fracture at < 60 year Other causes of osteoporosis, e.g. alcohol excess, RA, Hyperparathyroidism, thyrotoxicosis

 Osteoporosis: major complications of corticosteroid (CS)

therapy.
Patients with rheumatoid arthritis (RA) Hip, vertebral,

and distal forearm fractures.

In asthma Vertebral and rib fractures.

 In systemic lupus erythematosus Significant reductions

in lumbar spine and femoral neck BMD have been found in pre-menopausal patients.
In

inflammatory bowel disease

Prevalence of

osteopenia between 30 and 77%.

PATHOGENESIS
Mechanism of CIOP : Uncertain Different from that

of post-menopausal osteoporosis Major difference is

bone formation.
In post-menopausal osteoporosis: Reduction in trabecular

bone volume increase in bone resorption trabecular discontinuity

Reduction in trabecular bone volume decreased bone

formation in CIOP result of trabecular thinning.

DIAGNOSIS
In post-menopausal osteoporosis Risk of osteoporotic

fractures has been shown to be doubled for each standard deviation decrease in BMD This may underestimate the risk for patients treated with CS.
Quantitative ultrasound measurements to identify risk of

decreased BMD and increased fracture risk Widely

srudied in postmenopausal osteoporosis Data are still few in CIOP.

 Several non-invasive methods for skeletal assessment :

1.

BMD measurement by dual-energy X-ray absorptiometry (DXA)

2.

Broadband ultrasound attenuation (BUA)

3.

Biochemical markers of bone turnover.

Relationship between BMD and fractures has been

addressed

in

steroid-treated

population

BMD

measurements have been found to predict fractures relatively poorly

 Clinical risk factors indicate that the risk of developing

CIOP is increased: Decision to commence treatment can

be taken without a BMD measurement.

Measuring BMD Pre-treatment baseline to future

therapy .
In patients with no clinical risk factors for CIOP:

Measurement of BMD guides decision about starting

therapy.

It is recommended that all patients on CS should be advised to modify their lifestyle factors known to affect bone such as limiting cigarette smoking and alcohol consumption,

increasing weight-bearing activity as well as taking steps to

prevent falls.

Some of the risk factors that have been shown to be

effective in reducing the incidence of falls in non

institutionalized elderly like reduction in he use of sedative agents of benzodiazepines.

Primary prevention.
Primary prevention is treatment started at the time of initiation (up to 3 months) of CS therapy(1,2). Calcium supplementation, up to 1000 mg daily, alone is ineffective in preventing CS-induced bone loss. 1. Calcitriol. Dose of 0.6 mg per day, prevent bone loss at the lumbar spine, no effect at the femoral neck or distal radius. 2. Calcitonin. The results of using calcitonin has been conflicting. In the study by Sambrook et al, the addition of nasal calcitonin did not confer any additional protective effect. Healey et al. found that calcitonin was no better than calcium and vitamin D in protecting against Calcitriolualfacalcidol.

3. Fluoride. Lems et al. studied 44 patients with predominantly rheumatological diseases,

of whom 14 had just started CS. They found a 2.2% increase in lumbar spine
BMD after 2 year in the group taking sodium fluoride 25 mg twice daily with calcium compared with a 3% loss in the calcium-alone group. 4. Alendronate. In patients with sarcoidosis on CS, alendronate (5 mg daily) prevented bone loss at the ultradistal radius compared with a 4.5% loss in the placebo group over 1 year.

5. Pamidronate. Intermittent intravenous pamidronate has been shown to increase lumbar spine BMD by 3.6% and hip BMD by 2.2%

over 1 year compared with a 5.3% decrease at both sites in the

group on calcium alone. 6. Bisphosphonates. Cyclical etidronate therapy has been shown in several studies to be effective in the prevention of CIOP at the lumbar spine.

Secondary prevention.
Secondary prevention is treatment started >1 year after the initiation of CS therapy or following an osteoporotic fracture and implies established bone loss. 1. Calcium and vitamin D. Calcium and vitamin D was more effective than calcium alone or no therapy in the treatment of CIOP at the lumbar spine with a 3.2% difference in BMD between treatment and control. The doses: 400 IU daily to 50 000 IU/week .

2. Calcitriol. There are no studies using activated vitamin D metabolites in the

secondary prevention of CIOP.

3. Calcitonin. In a group of asthmatic patients, nasal calcitonin increased lumbar

spine BMD in the first year of treatment by 2.7% and maintained the
gain for a second year compared with a decrease in the placebo group over the 2 year. In CS-treated RA patients, nasal calcitonin prevented

femoral neck but not lumbar spine bone loss compared with calcium
alone.

4. Fluoride. Using sodium monofluorophosphate (100 mg twice daily) with calcium, there was an increase in lumbar spine BMD of 11%

compared with a 1.2% increase in the calcium-alone group after 2

year in 35 patients with respiratory diseases. 5. Bisphosphonates.

A recent meta-analysis concluded that bisphosphonates are effective

in the treatment of CIOP with an average percentage change in lumbar spine and femoral neck BMD of 4 and 2.1%, respectively, at 1 year.

6. Etidronate.

Several placebo-controlled studies have confirmed that

cyclical etidronate is effective in the treatment of CIOP. 7. Alendronate. A dose of 10 mg daily, has been shown to increase lumbar spine and femoral neck BMD by 2.9 and 1%, respectively,

compared with a decrease of 0.4 and 1.2%, respectively, in the

placebo group over 48 weeks in patients receiving CS therapy.

8. Pamidronate.

Intermittent intravenous pamidronate has been shown to

increase BMD at the lumbar spine by 19.6% (measured by quantitative CT) compared with a decrease of 8.8% in the calcium-alone treated group over 1 year. 9. Hormone replacement therapy.

HRT has been shown to increase lumbar spine BMD by 2.2

4.1%in CS-treated patients with asthma and RA.

 Physicians managing patients on CS should always

consider the need for therapy to prevent or treat CIOP.

Vitamin D products, HRT, fluoride, calcitonin and the

bisphosphonates: Effective to varying degrees in the prevention and treatment of CIOP, and maintaining or improving BMD.
All patients on CS modify lifestyle factors.

 Bisphosphonates: most promising class of agents in this

regard.
Comparison between therapeutic agents is complicated by

the variation in CS dose, varying therapeutic regimes and by small sample sizes without the power to study fracture

incidence.

1. Yeap SS, Hosking DJ. Management of Corticosteroid - Induced Osteoporosis. Rheumatology 2002; 41: 10881094. 2. Heaney RP. Calcium, Dairy Products and Osteoporosis. Journal of the American College of Nutrition 2000; 19: 83S-99S. 3. Heaney RP. Bone Health. American Journal of Clinical Nutrition. 1997; 85: 300S303S. 4. Shah SK. Prednisone-Induced Osteoporosis: An Overlooked and Undertreated Adverse Effect. JAOA Vol 106 2006; 11: 653-657. 5. Tobias JH. Management of steroid-induced osteoporosis: what is the current state of play? Rheumatology 1999; 38: 19820. 6. Miller GD, Jarvis JK, McBean LD. The Importance of Meeting Calcium Needs with Foods. Journal of the American College of Nutrition 2001; 20: 168S-185S. 7. Sambrook P, Birmingham J, Kelly P. Prevention of Corticosteroid Osteoporosis -- A Comparison of Calcium, Calcitriol, and Calcitonin. N Engl J Med Vol 328 1993; 17471752. 8. Reid DM. Corticosteroid-Induced Osteoporosis: Guidelines for Prevention. Are They Useful? British Journal of Rheumatology 1997; 36: 1035-1037.