PharmacologyTier 1Medical Sciences concept

Glucocorticoid-induced osteoporosis - distinguishing features

Core concept

The mechanism is different from postmenopausal osteoporosis, and so is the clinical behaviour
Dominant mechanism: suppression of bone FORMATION
- dec osteoblastogenesis (Wnt inhibition, inc sclerostin, inc DKK1), diversion of mesenchymal stem cells to adipocytes
- inc apoptosis of osteoblasts and osteocytes
Secondary contributions
- inc RANKL, dec OPG -> inc resorption, greatest in the first 3-6 months
- dec intestinal calcium absorption, inc urinary calcium -> secondary hyperparathyroidism
- Hypogonadism (dec GnRH/LH), myopathy -> falls

Feature	Glucocorticoid-induced
Bone lost first	Trabecular - vertebrae, ribs, proximal femur
Time course	Rapid: 6-12% in the first year, then ~3%/year
Fracture at a given BMD	Fractures occur at HIGHER BMD - bone quality, not just density
Bone turnover markers	Low formation (P1NP, osteocalcin) - a low-turnover state
Reversibility	Substantially reversible on stopping

DEXA underestimates the risk - FRAX must be adjusted upward for dose (FRAX assumes ~2.5-7.5 mg prednisolone; multiply hip fracture risk by ~1.2 and major osteoporotic by ~1.15 for higher doses)
No safe dose and no safe duration - risk rises from >=2.5 mg prednisolone daily and within 3 months of starting
- Risk is related to current dose more than cumulative, and falls after cessation
Inhaled and topical steroids carry much lower but non-zero risk at high dose
Assess every patient starting >=3 months of glucocorticoid
- Baseline DEXA, calcium, vitamin D, renal and liver function, testosterone in men, coeliac screen if indicated

Management

Universal: use the lowest effective dose and steroid-sparing agents; calcium 1000-1300 mg/day and vitamin D; weight-bearing exercise; fall prevention; smoking and alcohol
Start bone protection promptly - do not wait for a DEXA result in a high-risk patient
Pharmacotherapy if on >=7.5 mg prednisolone for >=3 months, or any dose with a prior fragility fracture, age >50 with low T-score, or high adjusted FRAX
- First-line: oral bisphosphonate (alendronate, risedronate) or zoledronic acid
- Teriparatide is superior to bisphosphonate for BMD and vertebral fracture in GIOP - the mechanism matches (an anabolic agent for a formation defect); reserve for high risk or fracture on a bisphosphonate
- Denosumab is an alternative, with the same rebound caveat on cessation
PBS in Australia subsidises bisphosphonates for GIOP at >=7.5 mg prednisolone for >=3 months with a T-score <= -1.5
Reassess DEXA at 12 months (more frequent than in postmenopausal osteoporosis)
Vertebral fractures in GIOP are often silent - consider lateral spine imaging or vertebral fracture assessment

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