Recent advances in the field of Glucocorticoid Induced Osteoporosis

Ambrish Mithal DM
Chairman and Head of Endocrinology and Diabetes, Max Healthcare, Saket, New Delhi

Changing paradigms and concepts

  • There is no “safe dose” or “safe duration” for glucocorticoids. For example, high dose intravenous methylprednisolone (up to 1 g) is not harmful to bone, but even a single oral dose of 2.5 mg of prednisone has an almost immediate negative effect on osteocalcin secretion.
  • There is no difference in daily vs alternate-day glucocorticoid administration as far as bone loss is concerned.
  • Inhaled glucocorticoids may be better than oral or systemic glucocorticoids in terms of bone health, but they still have their osseous tissue complications.
  • Bone turnover markers have limited role in prediction or diagnosis of GIOP. However, they can be used in treatment monitoring.

Do different Glucocorticoids carry different risks?

  • Although there are not many studies comparing equivalent doses of various steroids, it has been observed that dexamethasone causes more osteoporosis than other steroids as it is resistant to inactivation by 11β-HSD2.
  • Deflazacort is found to be less detrimental to bone, however, head-to-head comparison studies are limited.

Risk stratification for GIOP

  • Simple FRAX score cannot be used here as it is not valid for ages below 40 years; also, it uses femoral neck BMD, whereas GIOP predominantly affects the lumbar spine.
  • As per ACR guidelines, history of prior osteoporotic fracture, femoral/spine BMD, dose & duration of steroid and GC-adjusted FRAX score is used to categorise patients into high, moderate, and low fracture risk groups.
  • Pharmacological treatment is warranted for prevention as well as treatment of osteoporosis in moderate and high-risk groups.
  • For mild-risk groups with BMD (-1 to -1.5), if anticipated dose of prednisone is ≥7.5 mg/day or its equivalent, for duration a of ≥3 months, pharmacologic intervention is indicated.

Novel therapies for GIOP

  • After bisphosphonates, ACR recommends teriparatide and denosumab as second line therapies.
  • If these are not available, Raloxifene can be used for GIOP for men or for post-menopausal females.
  • Denosumab is under trials for paediatric GIOP.
  • Romosozumab (sclerostin inhibitor) is showing promising results in the on-going trials to prevent or reverse adverse skeletal effects of glucocorticoids.
  • Vamorolone is a “dissociative steroid” — it retains the beneficial anti-inflammatory activity of traditional glucocorticoid, but with a significant reduction in harmful effects. It is under phase 2 trials currently to replace steroids in Duchene muscular dystrophy.

How to prevent GIOP in Children

  • For GC-treated children, a calcium intake of 1,000 mg/day and vitamin D intake of 600 IU/day is recommended. However, the anti-fracture efficacy of these have limited evidence.
  • From a practical perspective, a 25-OHD level of 20 ng/mL is recommended through diet and supplementation.
  • Thus, the mainstay of prevention of GIOP in children is using least dose of steroids for least duration possible.
  • For children who have had an osteoporotic fracture, who continue glucocorticoid treatment at a dose of > 0.1 mg/kg/day for > 3 months, treatment with an oral or IV bisphosphonate is recommended.