Glucocorticoid induced osteoporosis (GIO)

Support us:

Support you by Becoming a YouTube member (Click here).
- Premium Membership- Download PDF version of Notes, Get ad free video and more
- Consultant Membership- Above plus Download Powerpoint presentation of the notes and get access to EndoAI for Free
Support us by purchasing our book - Click here for more details:
- Volume 1- THE BEST OF NOTES IN ENDOCRINOLOGY BOOK SERIES
- Volume 2- THE BEST OF NOTES IN ENDOCRINOLOGY - DIABETES SPECIAL

Credits
- Section Writer: Dr. Om J Lakhani
- Section Editor: Dr. Om J Lakhani
For corresponding notes for patients in simple language, please click the link below
- Impact of Steroids on bones
Q. Summarize the effect of Glucocorticoids on bones ?
- Calcium
  - Reduce calcium resorption from kidney
  - Reduce calcium absorption from intestine
- Bone cells
  - Enhance osteoblast apoptosis
  - Reduce OPG increase osteoclasts activity
- Other hormones
  - Suppress Estrogen/testosterone increase bone resorption
  - Suppresses GH-IGF1 axis → reduces bone formation
Q. What is the effect of Glucocorticoids on bone turnover ?
- Early – increased bone resorption
- Later – mainly affects bone formation
Q. Is secondary hyperparathyroidism a part of the pathogenesis of Glucocorticoid induced osteoporosis (GIO) ?
- No
- Recent data and literature suggest that PTH is not part of GIO
Q. What is the difference between Thyroxin and Glucocorticoids – both of which cause bone loss ?
- Thyroxine bone loss → but also produces secondary hyperparathyroidism → increase bone formation
- Glucocorticoids inhibits bone loss as well as bone formation → there is no secondary hyperparathyroidism
#Clinicalpearl
- As time passes- suppression of bone formation is the predominant effect in GIO
Q. What type of fracture are particularly common with GIO ?
- Vertebral fractures
Q. What does Osteoprotegrein (OPG) do ?
- OPG inhibits osteoclast formation and differentiation
Q. What is the effect of Glucocorticoids on OPG ?
- It reduces OPG hence enhancing osteoclasts differentiation
Q. On which bone cells are Glucocorticoids receptors present ?
- They are present on osteoblast and they enhance osteoblasts apoptosis
- They are not present on osteoclast-→ hence via OPG inhibition- they actually increase osteoclast activity early on
Q. Summarize the effect of Glucocorticoids on bone cells ?
- Glucocorticoids inhibit osteoblast directly → reduce bone formation
- Glucocorticoids → reduce OPG, increase RANKL activate osteoclast → increase bone resorption
- Hence net increase resorption without increase bone formation
Q. What is the mechanism of osteonecrosis secondary to Glucocorticoids ?
- Apoptosis of osteoblasts causes osteonecrosis
Q. What is the effect of Glucocorticoids on calcium metabolism ?
- Increases urinary calcium excretion
- Reduces calcium absorption from intestine
- Basically action opposite to vitamin D
Q. Is there any dose of Glucocorticoids which is safe in terms of bones ?
- Probably not
- Studies have shown at doses as low as 2.5 mg/day of prednisolone have an effect on bone
Q. Is alternate-day regimen protective of bone ?
- No
Q. Is physiological Glucocorticoids in adrenal insufficiency also associated with bone loss ?
- Yes
- Even the physiological replacement in AI produces bone loss
Q. Do inhaled steroids also produce bone loss ?
- Studies have not consistently shown that they also impact the bone
**CLINICAL FEATURES **
Q. What is the most common clinical presentation of GIO ?
- They most often present with Asymptomatic vertebral fracture – often within 3-6 months of therapy
Q. Do patients having Glucocorticoids have increased fracture risk beyond the same T score ?
- Yes
- For the same T score- patient taking Glucocorticoids have an increased risk of fractures
Q. Why is vertebral fracture more common in GIO ?
- Vertebral fracture are more common in patients on Glucocorticoids
- This is because Glucocorticoids have more effect on trabecular bone and vertebra have more trabecular bone
**Evaluation **
Q. Which patient taking Glucocorticoids to require assessment ?
- Any patient taking Glucocorticoids of any dose for duration >3 months or anticipated duration >3 months require assessment
Q. Which patients on Glucocorticoids require BMD assessment at baseline ?
- All patients receiving Glucocorticoids or about to receive Glucocorticoids with duration/anticipated duration >3 months for any dose of Glucocorticoids require a DEXA for BMD
Q. How much vitamin D is given to a patient with normal vitamin D and taking Glucocorticoids ?
- 800 IU/day
Q. Why is vertebral imaging important for patient on Glucocorticoids ?
- Vertebral fracture are common
- They are often asymptomatic
- They are markers of risk of other fractures
- It is also an indication for pharmacological therapy
Q. Which patients require vertebral imaging ?
- If the patient already indicates Pharmacological therapy – then no need for vertebral imaging
- However, if the patient per se does not have indication for pharmacological therapy (say T score of -1 to -2.5) – then a vertebral imaging will help establish the need for therapy
Q. How is vertebral fracture diagnosed ?
- Xray
- Vertebral fracture assessment tool – present on DEXA machines – better because no separate X-ray appointment needed
**PREVENTION AND TREATMENT **
Q. Give a outline for management of GIO ?
- STEP1 – BASELINE ASSESSMENT
  - 1. Note the dose and duration of Glucocorticoids intake
  - 1. Baseline DEXA scan for BMD
  - 1. Xray of LS spine AP /Lateral or DEXA vertebral fracture assessment for :
    - a. Not required for those already indicating Glucocorticoids use. Needed for the following :
      - i. T score -1.0 to -2.5
      - ii. Not having a history of fragility fracture
      - FRAX risk score calculation
      - Baseline blood investigations
    - a. Vitamin D
    - b. Serum calcium
    - c. Serum phosphorous
    - d. Testosterone and LH in males
    - e. Estrogen and FSH/LH in females
- STEP 2- General advice
  - 1. Avoid falls
  - 1. Correct vitamin D deficiency If present
  - a. Vitamin D -800 IU/day of vitamin D is normal
  - 1. Calcium – 1200 mg/day
  - 1. Avoid smoking
  - 1. Alcohol restriction
  - 1. Weight-bearing exercise as tolerated
- STEP 3- Hormone replacement
  - 1. Testosterone / estrogen replacement in male/females if evidence of hypogonadism and no contraindications
- STEP 4- Preventive/treatment indication for GIO
- STEP 4.1- Postmenopausal women / men >50 years of age
- Step 4.1.1 Categorize risk- based on FRAX
  - 1. High risk – FRAX >20%
  - 1. Moderate risk – FRAX- 10-20%
  - 1. Low Risk- FRAX <10%
- Step 4.1.2 – Medications
  - 1. High risk
  - a. Consider Teriparatide if :
    - i. If dose of Glucocorticoids>5 mg or prednisolone for <1 month
    - ii. Any dose of Glucocorticoids but duration >1 month
  - b. In other cases Alendronate/ Zolendronate can be given
  - 1. Moderate and low risk
  - a. Bisphosphonate therapy if the anticipated duration of Glucocorticoids is >3 months in dose >7.5 mg equivalent of prednisolone
- Step 4.1.3- Follow up
  - 1. Annual DEXA scan to be done
  - 1. If DEXA shows no decline in BMD- Then repeat every 1-2 years
  - 1. If Glucocorticoids is stopped – consider stopping the medication is no other cause for osteoporosis exists
- Step 4.2- Men age <50 years and Premenopausal women not having fertility potential
  - 1. Patients not having fragility fracture- no indication
  - 1. Patients having fragility fracture
  - a. Glucorticoid duration 1-3 months- consider therapy if dose of Glucocorticoids> 5 mg equivalent of prednisolone
  - b. Glucocorticoids duration >3 months- consider therapy irrespective of the dose
- Step 4.3- Premenopausal women with fertility potential
  - 1. Patients not having fragility fracture- no indication
  - 1. Patients having fragility fracture
  - a. Glucorticoid duration 1-3 months- No indication
  - b. Glucocorticoids duration >3 months- consider therapy only for dose of prednisolone >7.5 mg . Avoid Zolendonate.
Q. What dose of calcium and vitamin D are recommended for patient on Glucocorticoids ?
- Calcium – 1200mg/day
- Vitamin D- 800 IU/day
Q. Should FRAX be calculated in all patients with Glucocorticoids ?
- No
- If the patient is already a candidate for Pharmacological therapy based on BMD and/or history of previous vertebral fracture than FRAX is not required
- However, if the patient is not a candidate for pharmacological therapy then FRAX is indicated
Q. what FRAX score suggests a high risk of fracture ?
- More than 20% for any fracture
- More than 3% for hip fracture
Q. Is FRAX and BMD enough ?
- No
- FRAX and BMD will not diagnose all patients with Glucocorticoids are risk of treatment
- Remember – the patients on Glucocorticoids are at risk of fracture beyond that suggested by BMD
- Also FRAX underestimates the risk of vertebral fracture which is common in patients taking Glucocorticoids
- Hence FRAX and BMD both will underestimate the risk
Q. Is Glucocorticoids a component of FRAX risk score calculation ?
- Yes
Q. According to ACR (American College of Rheumatology) guidelines, which are 3 groups for GIO ?
- Three groups
  - Post menopausal / men >50 years
  - Men <50 years / premenopausal women – no fertility potential
  - Premenopausal women with fertility potential
**Choice of therapy **
Q. What is a choice of therapy by uptodate for men > 50 and postmenopausal women ?
- Oral bisphosphonate is first choice
- Zoledronate given if oral not tolerated
- Teriparatide for
  - T score <-3.5
  - T score <-2.5 + fragility fracture
Q. What about premenopausal women ?
- Oral bisphosphonates – preferred
- Zoledronate- avoided
- Teriparatide- can be used if epiphysis have fused
Q. Which is the probably the best drug to use in the treatment of GIO ?
- Teriparatide
- This is because GIO is a low turnover disease with reduced bone formation
- Hence teriparatide is very useful in this disorder
Q. Which is better for GIO- teriparatide or bisphosphonate ?
- Study done by Saag et al showed better response with teriparatide compared to Bisphosphonate in terms of improvement in BMD at 18 and 36 months
- Also in terms of vertebral fractures were less in teriparatide arm
Q. Is hormone replacement advised ?
- It patient is hypogonadal as a result of the Glucocorticoids and there are no contraindications, hormone replacement is advised
Q. What happens after discontinuation of Glucocorticoids ?
- There is improvement in BMD
Q. What are the guidelines for monitoring a patient with GIO on treatment ?
- BMD at baseline and one year after starting therapy
- If BMD has improved or stable- less frequent monitoring may be required
- If Glucocorticoids are discontinued and BMD is stable- monitoring every five years may be enough
#Clinicalpearl
- Glucocorticoids are the most common etiology of secondary drug-induced osteoporosis
Q. What are the guidelines for BMD monitoring in patients on Glucocorticoids ?
- All patients on Glucocorticoids – before starting Glucocorticoids and while taking Glucocorticoids must undergo BMD
- This must be repeated every six months
Q. Is COPD itself associated with osteoporosis?
- Yes
- 30-60% of patient with COPD have osteoporosis

Please consider donating to "Notes in Endocrinology" to keep us going. Please visit our DONATION page to know more