CORTICOSTEROIDS

See also under "Asthma and COPD" regarding inhaled corticosteroids

I. Side effects of systemic use (tend to be worse in elderly):

1. Short-term:
   1. Hyperglycemia
   2. Increased appetite
   3. Mood alteration
   4. HTN
2. Long-term
   1. Adrenal suppression
   2. Peptic Ulcer Disease--In a case-control study of 2,105 pts with gastric or duodenal bleed vs. 11,500 controls, after adjusting for potential confounders, current corticosteroid use was ass'd with RR 1.8 (sig.) for UGI bleeding (Am. J. Epidemiol. 153:1089, 2001--JW)
   3. Osteoporosis
   4. Aseptic necrosis of femur (rare)
   5. Growth suppression (controversial whether occurs with inhaled steroids)
   6. Dermal thinning
   7. Cushing's syndrome
   8. Cataracts
   9. Muscle weakness
   10. Immunosuppression; tend to be worse in the elderly
   11. Difficulty w/ "explicit" but not "implicit" memory (Neurology 47:1396, 1996-JW)

II. Side effects of tpoical use:

1. Skin atrophy
2. Striae
3. Telangiectasias
4. Hypopigmentation
5. Systemic absorption when used over large skin area

III. Guidelines for chronic systemic use:

1. Alternate-day dosing may produce less toxicity than every day
2. Prevention of steroid-induced osteoporosis
   1. Concurrent use of Ca supplements, vitamin D, and where appropriate, estrogen replacement; esp. in elderly
   2. Etidronate for prevention of corticosteroid-induced osteoporosis (NEJM 337:382, 1997--UW Pharm letter)
      1. 122 men & women who had recently started high-dose systemic steroid Rx, mostly for rheumatoid arthritis
      2. Randomized to etidronate vs. placebo x 14d followed by Ca x 76d, given x 4 cycles
      3. At 1y, lumbar spine and trochanteric bone density sig. higher in etidronate group (sl. increase vs. sl. decrease)
      4. Sig. decrease in new vertebral fx amone the postmenopausal women
   3. Alendronate for prevention of corticosteroid-induced osteoporosis
      1. 447 pts 17-83yo taking prednisone avg. 10mg/d randomized to alendronate 5-10mg/d vs. placebo x 48wks; all pts also got vit. D and Ca. Alendronate group had sig. higher lumbar spine, femoral neck, and trochanteric bone density. No sig. diff. in vertebral fx (low incidence in both groups) (NEJM 339:292, 1998--JW)
      2. An extension of the above-mentioned study fo 2y post-randomization found Alendronate ass'd with sig. lower incidence of new vertebral fx (0.7% vs. 6.8%) and nonsig. lower risk of nonvertebral fx (5.4% vs. 9.8%) (Arth. Rheum. 44:202, 2001--JW)
   4. Risedronate for prevention of corticosteroid-induced osteoporosis
      1. 228 pts on oral steroids for < 3mos (mean dose 21mg/d prednisone), avg. age 60, randomized to risedronate 2.5-5mg/d vs. placebo. At 1y f/u, change in BMD was sig. diff. for all 3 groups (dec. 3% for placebo, no change in 2.5mg/d group, 1% higher in 5mg group); also, pts on placebo were nonsig. more likely to be dx'd with new vertebral fx (Arth. Rheum. 42:2309, 1999--JW)
3. NHLBI reccs bone densitometry at initiation of chronic systemic steroids and again 6mo later in pts who are at risk for accelerated bone loss (pre-existing osteoporosis, postmenopausal female, sedentary, etc.); this approach has not been evaluated in clinical trials as of 1997