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Chronic Glucocorticoid Therapy-Induced

Osteoporosis in Patients with Persistent

Asthma and Chronic Obstructive Pulmonary
Disease (CPOD)

Edu Tehupeiory



• Long-term glucocorticoid (GC) therapy has been

decreasing morbidity and mortality in of chronic
inflammatory disease.
• Persistent asthma and COPD.
• The important and often unrecognized side
effects is secondary osteoporosis.
Risk Factors

• The risk of GC – Induced bone loss is correlated

with : daily dose, duration and total cummulative
lifetime dose of GC treatment.
• Oral prednisone increase the risk of bone loss
and fracture.
• High doses of inhaled GCs may also increased
the risk of Osteopenia / Osteoporosis.

1. Moleculer Biology of CS Action

- CS exert their effects, anti-inflammatory and
immunosuppressive primarily through
interaction with ubiquitously receptors.
- In the circulation : free form and association
with cortisol-binding globulin.
- Free form diffuses through plasma
membrane  bind the cytoplasmic CS
- The formation of steroid receptor complex
 followed by translocation of the complex to
the nucleus.
- Corticosteroids regulate gene expression by :
transcriptional, post transcriptional, and post-
translational mechanism.
2. Cellular Effects of CS
- CS influence the function of variety of organs
and their component cells.
- Effects of CS on particular cell type depends
on concentration and type of CS
(synthetic / naturally occuring and the receptor
subtype to which steroid binds).
• The outcome varies with the phase in the cell
cycle and stage of differentiation or activation of
the cells.
GC - Dose

• In patients treated with oral GC more than

1 year, 86 % demonstrated a decrease in bone
mineral (dose not stated).
• Daily dose :
Low - dose : 33 % decrease BMD
Medium - dose : 71 % decrease BMD
High - dose : 80 % decrease BMD
Clinical Importance of
GC induced OP
• Most common form of drug – related OP in men
and women.
• Occurs at any age, in both gender, across races.
• Up to 50 % of patients on chronic steroid therapy
sustain OP fractures and/or develop
GC Induced OP
• Corticosteroids induce OP primarily through
effects on bone synthesis or formation.
• Bone remodeling is regulated via the interaction
of systemic hormones and local cytokine.
• An inbalance between osteoblast activity.
• Metabolic abnormalities contribute increased
bone absorption.
*) Secondary hyperparathyroidism.
*) Decrease adrenal production of androgene.
• The severity of these side effects parallels other
• Incidence is uncertain, approx 30 – 90 % and
the severity of OP is closely related to dose and
duration of GC therapy.
• Bone loss is greatest during the first 6 to 12
months of therapy and most marked in
trabecular bone.
• Additional factors that accelerate the risk
of fracture
- Smoking, alcohol intake
- Sedentary lifestyle, diet low calcium and
vit – D
- Menopause
• Fundamentaly GC are catabolic hormones,
acting through the GC receptor.
• Reduce the transcription of mRNAs for the
various constituent of bone matrix such as type
1 collagen
• Corticostiroid have important effects on bone
through indirect suppression of gonadal and
adrenal androgen production and secretion.
• Inhibit intestinal calcium absorption  promote
renal calcium excretion.
• This net calcium loss stimulates PTH secretion
 secondary hyperparath, which additional
contributes to bone loss.
• Plasma levels of PTH increased in most patients
taking high dose of GC.
• The major effect of corticosteroids is the

• Early detection of bone loss prior to clinical

manifestafiosis is paramount.
• Conventional radiology not sensitive to detect
early bone loss.
• Changes less than 30% in bone density, cannot
be detected by conventional radiographic
• Biochemical markers.
- Bone formation :
(osteocolein, alkalin phosphatase, bone
APh, procollagen type I carboxy-terminal
propeptide (PICP))
- Bone resorption :
(hydroxyproline, pyridoline, deoxypyridinoline)
• Biochemical markers in monitoring response to
• Dual Energy X-ray Absorptiometry (DXA) scans
of the lumbar spine, hip, or wrist provide reliable
assessment of BMD and predict the risk of future
• DEXA “Gold Standard” for diagnosis

• Attemps to reduce the risk of bone loss :

- Use the lowest effective oral/inhaled GC dose.
- Optimal use of alternative non-GC anti-inflam
matory drugs.
• Modification Lifestyle :
- Smoking cessation.
- Reduced/stop alcohol intake.
- Prevention of falls.
Treatment Recommendation

1. - For the prevention of GC-Induced bone loss in

adult patient beginning or currently recieving
long-term GC (oral and/or inhaled) assessment
of lumbar spine or femoral (neck BMI).
- Standard lateral thoracic and lumbar spine
radiographs should be obtained.
- If no fracture and BMD is normal : adequate
calcium and vitamin-D (800 IU/d)
- These supplements impede the proggression
to osteopenia.
- After one month of supplementation, 24-h urine
calcium should be assessed  Hypercalciuria.
- If present, hypercalciuria require treatment with
calcium-sparing diuretic (e.g : indopamide 1.25
mg/d trichlormethiazide 2.0 mg/d)
2. Patients with long-term GC documented bone
loss and/or osteoporotic fracture :
- Supplement calcium & vitamin-D.
- HRT (Not approved in USA).
- Bisphosphonate therapy.
Risedronate in the Prevention of CIO:

 In patients initiating oral corticosteroids,

risedronate prevents bone loss with a trend in
reducing vertebral fractures
 Risedronate protects against loss of both
cortical and trabecular bone
 Risedronate was well-tolerated and exhibited
a favorable bone safety profile

Cohen at al, Arthritis and Rheumatism, 1999

3. - After initiation of treatment BMD assessment
every 12 month.
- If BMD remains stable (increasing relative to
baseline or decreasing by less than 5 %), no
therapeutic changes .
- If BMD declines by > 5 %, pharmacologic
- Consultation with a bone metabolism specialist.
to therapy.

Reducing prevalance of GC-Induced bone loss in

patients with asthma and COPD, require the
1. The appropriate use of NSAID to limit
exposuren to GC.
2. Understanding of the adverse effects of
chronic oral and inhaled GC therapy.
3. Early identification of asthma and COPD
4. Utilization of agents attenuate bone resorption
and promote bone formation.
5. Ability to quickly, precisely, and inexpensively
assess improvements in BMD in respons to