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This document discusses chronic glucocorticoid therapy-induced osteoporosis in patients with persistent asthma and chronic obstructive pulmonary disease. It covers risk factors for glucocorticoid-induced bone loss including daily dose, duration, and total lifetime dose. It also discusses molecular mechanisms, cellular effects, importance of glucocorticoid-induced osteoporosis, diagnosis using biomarkers and DEXA scans, and treatment recommendations including calcium, vitamin D, bisphosphonates, and lifestyle modifications.
This document discusses chronic glucocorticoid therapy-induced osteoporosis in patients with persistent asthma and chronic obstructive pulmonary disease. It covers risk factors for glucocorticoid-induced bone loss including daily dose, duration, and total lifetime dose. It also discusses molecular mechanisms, cellular effects, importance of glucocorticoid-induced osteoporosis, diagnosis using biomarkers and DEXA scans, and treatment recommendations including calcium, vitamin D, bisphosphonates, and lifestyle modifications.
This document discusses chronic glucocorticoid therapy-induced osteoporosis in patients with persistent asthma and chronic obstructive pulmonary disease. It covers risk factors for glucocorticoid-induced bone loss including daily dose, duration, and total lifetime dose. It also discusses molecular mechanisms, cellular effects, importance of glucocorticoid-induced osteoporosis, diagnosis using biomarkers and DEXA scans, and treatment recommendations including calcium, vitamin D, bisphosphonates, and lifestyle modifications.
Asthma and Chronic Obstructive Pulmonary Disease (CPOD)
Edu Tehupeiory
SUB-BAGIAN REUMATOLOGI BAGIAN ILMU PENYAKIT
DALAM FAKULTAS KEDOKTERAN UNIVERSITAS HASANUDDIN MAKASSAR INTRODUCTION
• 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. CORTICOSTEROID (CS)
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 receptor. - 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 osteonecrosis. PATHO – PHYSIOLOGY of 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 effects. • 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 INHIBITION OF BONE FORMATION DIAGNOSIS
• 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 imaging. • 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 therapy. • 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 fracture. • DEXA “Gold Standard” for diagnosis osteoporosis. THERAPIES FOR THE TREATMENT OF GC-INDUCED OSTEOPOROSIS.
• 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: Conclusions
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 changes. - Consultation with a bone metabolism specialist. to therapy. SUMMARY
Reducing prevalance of GC-Induced bone loss in
patients with asthma and COPD, require the following. 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 patients 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 therapy.