Glucocorticoid-induced Osteoporosis Treatment Guidelines

Various Glucocorticoid-induced Osteoporosis Treatment Guidelines have been published. The American College of Rheumatology guidelines for the prevention and treatment of Glucocorticoid-induced osteoporosis are presented here.


Prior to the recommendations made by the ACR experts, let's define and classify patients into different risk groups:

Fracture risk categories in glucocorticoid treated patients:

  • Low fracture risk:

    • Adults less than 40 years of age:

      • GC treatment at a dose of 7.5 mg/day or less for less than 6 months
    • Adults 40 years of age or more:

      • GC-adjusted FRAX 10-year risk of major osteoporotic fracture less than 10%
      • GC-adjusted FRAX 10-year risk of hip fracture 1% or less.
  • Moderate fracture risk:

    • Adults <40 years of age:

      • Hip or spine bone mineral density Z score of less than - 3 or
      • rapid bone loss of 10% or more at the hip or spine over 1 year and Continuing GC treatment at a dose of 7.5 mg/day or more for 6 months or more
    • Adults 40 years of age or more:

      • GC-adjusted FRAX 10-year risk of major osteoporotic fracture 10–19%
      • GC-adjusted FRAX 10-year risk of hip fracture > 1% and < 3%
  • High fracture risk:

    • Adults less than 40 years of age:

      • Prior osteoporotic fracture
    • Adults 40 years of age or greater:

      • Prior osteoporotic fracture
      • Hip or spine bone mineral density T score of less than - 2.5 in men aged 50 years or more and postmenopausal women
      • GC-adjusted FRAX 10-year risk of major osteoporotic fracture of 20% or more
      • GC-adjusted FRAX 10-year risk of hip fracture of 3% or more.

 

Major Osteoporotic Fracture is a fracture at the spine, hip, wrist, or humerus

FRAX score is calculated online (https//www.shef.ac.uk/FRAX/tool.jsp.)


Recommendations for fracture risk assessment and reassessment:

Initial fracture risk assessment.

All patients should have an initial clinical fracture risk assessment as soon as possible and preferably within 6 months of the initiation of long-term glucocorticoid treatment.

This assessment should include:

  • a history with the details of glucocorticoid use:

    • dose,
    • duration,
    • the pattern of use
  • an evaluation for:

    • falls,
    • fractures,
    • frailty
  • other risk factors for fracture:

    • malnutrition,
    • significant weight loss or low body weight,
    • hypogonadism,
    • secondary hyperparathyroidism,
    • thyroid disease,
    • family history of hip fracture,
    • history of alcohol use or smoking and
    • other clinical comorbidities
  • a physical examination including:

    • measurement of weight and height (without shoes),
    • testing of muscle strength, and
    • assessment for other clinical findings of undiagnosed fracture (i.e., spinal tenderness, deformity, and reduced space between lower ribs and upper pelvis) as appropriate given the patient’s age.

In addition, Adults aged 40 years or more, the initial absolute fracture risk assessment should be done using

FRAX (https://www.shef.ac.uk/FRAX/tool.jsp)

with the adjustment for glucocorticoid dose and BMD testing (if available, or without BMD if it is not available) as soon as possible, but at least within 6 months of the initiation of glucocorticoid treatment. For adults less than 40 years of age, bone mineral density testing should be done as soon as possible but at least within 6 months of the initiation of glucocorticoid treatment if:

  • the patient is at high fracture risk because of a history of previous osteoporotic fracture or
  • if the patient has other significant osteoporosis risk factors like:
    • malnutrition,
    • significant weight loss or low body weight,
    • hypogonadism,
    • secondary hyperparathyroidism,
    • thyroid disease,
    • family history of hip fracture,
    • smoking,
    • alcohol use.

[caption id="attachment_9433" align="aligncenter" width="935"]glucocorticoid induced osteoporosis treatment guidelines Fracture risk initial assessment - glucocorticoid-induced osteoporosis treatment guidelines[/caption]


When should the individuals be reassessed for fracture risk?

All individuals who continue long term glucocorticoid treatment, a clinical fracture reassessment should be done every year.

Adults 40 years of age or more

For adults 40 years of age or more who continue glucocorticoid treatment and are not treated with an osteoporosis medication beyond calcium and vitamin D, a reassessment should be done using FRAX (with BMD testing if available) every 1–3 years.

Patients aged 40 years or more who are receiving very high doses of glucocorticoid (30 mg or more per day or a cumulative dose of more than 5 gms in the last one year) or those with a history of osteoporosis fracture should have fracture reassessment performed earlier within this 1–3-year time.

Individuals 40 years of age or more using lower doses of glucocorticoids and without a history of osteoporotic fractures should have less frequent testing of fracture reassessment.

For adults 40 years of age or older who continue glucocorticoid treatment and are being treated with an osteoporosis medication in addition to calcium and vitamin D, BMD testing should be completed every 2–3 years during treatment in high-risk patients such as:

  • those receiving very high-dose of glucocorticoids (prednisone dose 30 mg/day or more or a cumulative dose greater than 5 gm in the previous year),
  • a history of osteoporotic fracture occurring 18 months or more of treatment with anti-fracture medication (other than calcium and vitamin D),
  • risks for poor medication adherence or absorption, or
  • other significant OP risk factors.

For adults 40 years of age or more who received osteoporosis treatment in the past but are no longer being treated with an osteoporosis medication other than calcium and vitamin D, BMD testing should be done every 2–3 years.

Adults less than 40 years of age.

For all adults, less than 40 years of age who continue glucocorticoid treatment and are at moderate-to-high fracture risk:

  • history of the previous fracture, BMD Z score of less than -3,
  • received very high-dose prednisone equivalent or greater than 30 mg/day and cumulative dose of greater than 5 gm in the previous year,
  • risks for poor medication adherence or absorption, or
  • multiple osteoporosis risk factors, BMD testing should be done every 2–3 years.

[caption id="attachment_9432" align="aligncenter" width="939"]glucocorticoid induced osteoporosis treatment guidelines Fracture risk reassessment - glucocorticoid-induced osteoporosis treatment guidelines[/caption]


Glucocorticoid-induced Osteoporosis Treatment Guidelines - Recommendations for the initial treatment in adults (women not of child-bearing potential and men) initiating long-term GC treatment

All adults taking prednisone at a dose of 2.5 mg/day or more for 3 months or more:​​​​​​​

  • Optimize calcium intake (1,000–1,200 mg/day) and vitamin D intake (600–800 IU/day) and lifestyle modifications as given below over no treatment or over any of these treatments alone.
    • a balanced diet,
    • maintaining weight in the recommended range,
    • smoking cessation,
    • regular weight-bearing or resistance training exercise,
    • limiting alcohol intake to 1–2 alcoholic beverages/day

Conditional recommendation because of

  • indirect evidence (on the impact of lifestyle changes on fracture risk and the benefit of calcium and vitamin D on fracture risk in general patients with osteoporosis)
  • low-quality evidence (on the impact of calcium and vitamin D on fractures in glucocorticoid users)

Adults age 40 years or more at low risk of fracture:

  • Calcium and vitamin D intake should be optimized along with lifestyle modification rather than treatment with bisphosphonates, teriparatide, denosumab, or raloxifene.

Conditional recommendation for calcium and vitamin D over oral bisphosphonates, teriparatide, and denosumab because of low-quality evidence on the additional anti-fracture benefit of the alternative treatments in this low-risk group, costs, and potential harms

Strong recommendation for calcium and vitamin D over IV bisphosphonates and raloxifene because of low-quality evidence on additional anti-fracture benefit in this low-risk group and their potential harms


Adults age 40 years or more at moderate risk of major fracture​​​​​​​

  • Treat with an oral bisphosphonate rather than calcium and vitamin D alone.
  • Treat with an oral bisphosphonate rather than intravenous bisphosphonates, teriparatide, denosumab, or raloxifene.
  • Oral bisphosphonates preferred for safety, cost, and because of the lack of evidence of superior anti-fracture benefits from other OP medications.
  • If oral bisphosphonates are not appropriate, other therapies recommended in order of preference include:
    • IV bisphosphonates

    • Teriparatide

      • Cost and burden of therapy with daily injections
    • Denosumab

      • Lack of safety data in people treated with immunosuppressive agents
    • Raloxifene (for postmenopausal women in whom none of the medications listed above is appropriate)

      • Lack of adequate data on benefits (impact on the risk of vertebral and hip fractures in GC users) and potential harms (clotting risks, mortality)

Conditional recommendations because of indirect and low-quality evidence comparing the benefits and harms of alternative treatments in people with moderate fracture risk


Adults age 40 years or more at high risk of fracture​​​​​​​

  • Oral bisphosphonate should be used rather than calcium and vitamin D alone.
  • Oral bisphosphonate should be used rather than intravenous bisphosphonates, teriparatide, denosumab, or raloxifene.
  • Oral bisphosphonates preferred for safety, cost, and because of the lack of evidence of superior anti-fracture benefits from other OP medications.
  • If oral bisphosphonates are not appropriate, other therapies that may be used in the order of preference:
    • Intravenous bisphosphonates

      • The higher risk profile for IV infusion over oral bisphosphonate therapy
    • Teriparatide

      • Cost and burden of therapy with daily injections
    • Denosumab

      • Data are lacking regarding its safety in people treated with immunosuppressive agents
    • Raloxifene (for postmenopausal women in whom other medications may be inappropriate)

      • Lack of adequate data on benefits (impact on the risk of vertebral and hip fractures in GC users) and potential harms (clotting risks, mortality)

Strong recommendation for oral bisphosphonates over calcium and vitamin D alone because of the strength of the indirect evidence of anti-fracture efficacy and low harms

All other recommendations conditional because of indirect and low-quality evidence comparing the benefits and harms of alternative treatments in people with high fracture risk


Adults aged less than 40 years at low risk of fracture

  • Calcium and vitamin D intake should be optimized along with lifestyle modifications over treatment with bisphosphonates, teriparatide, or denosumab.

Conditional recommendation for calcium and vitamin D over oral bisphosphonates, teriparatide, and denosumab because of low-quality evidence on the additional anti-fracture benefit of the alternative treatments, costs, and potential harms

Strong recommendation for calcium and vitamin D over IV bisphosphonates because of low-quality evidence for additional anti-fracture benefit in this low-risk group and potential harms


Adults aged less than 40 years at moderate-to-high risk of fracture​​​​​​​

  • Treat with an oral bisphosphonate rather than calcium and vitamin D alone.
  • Treat with an oral bisphosphonate rather than intravenous bisphosphonates, teriparatide, or denosumab.
  • Oral bisphosphonates preferred for safety, cost, and because of the lack of evidence of superior anti-fracture benefits from other OP medications.
  • If oral bisphosphonates are not appropriate, other therapies that may be used in order of preference include:
    • IV bisphosphonates

      • The higher risk profile for IV infusion over oral bisphosphonate therapy
    • Teriparatide

      • Cost and burden of therapy with daily injections
    • Denosumab

      • Data regarding its safety are limited in people treated with immunosuppressive agents

Conditional recommendations because of low- to very low-quality evidence on absolute fracture risk and indirect and low-quality evidence comparing relative harms and benefits of alternative treatments in this age group

[caption id="attachment_9431" align="aligncenter" width="763"]glucocorticoid induced osteoporosis treatment guidelines glucocorticoid-induced osteoporosis treatment guidelines[/caption]


Recommendations for initial treatment for the prevention of glucocorticoid-induced osteoporosis in special populations of patients beginning long-term glucocorticoid treatment

  • Women of childbearing potential at moderate-to-high risk of fracture who do not plan to become pregnant within the period of OP treatment and are using effective birth control or are not sexually active:

    • Treatment with an oral bisphosphonate is preferred over calcium and vitamin D alone, teriparatide, intravenous bisphosphonates, or denosumab.
    • Oral bisphosphonates preferred for safety, cost, and because of the lack of evidence of superior anti-fracture benefits from other OP medications.
    • If oral bisphosphonates are not appropriate, other therapies in order of preference include:
      • Teriparatide

        • Cost, safety, and burden of therapy with daily injections
        • Consider the following therapies only for high-risk patients because of a lack of safety data on the use of these agents during pregnancy:
        • IV bisphosphonates

          • Potential fetal risks of intravenous infusion during pregnancy
        • Denosumab

          • Potential fetal risks during pregnancy

Conditional recommendations (very low-quality evidence on benefits and harms of these treatments to the fetus during pregnancy)


Adults age 30 years or more and receiving very high-doses of glucocorticoids (initial dose of prednisone >/= 30 mg/day and cumulative dose >5 gm in one year)

Conditional recommendations (low-quality evidence on absolute fracture risk and harms in this population)


Adults with organ transplant, glomerular filtration rate of 30 ml/minute or more, and no evidence of metabolic bone disease who continue treatment with Glucocorticoids

  • Treat according to the age-related guidelines for adults without transplants, with these additional recommendations:
    • An expert should evaluate all these patients.
    • Denosumab should not be used due to inadequate safety data on infections in adults treated with multiple immunosuppressive agents.

Conditional recommendations because of low-quality evidence on anti-fracture efficacy in transplant recipients and on relative benefits and harms of the alternative treatments in this population


Children ages 4–17 years treated with GCs for >/= 3 months

  • Calcium intake (1,000 mg/day) and vitamin D intake (600 IU/day) should be optimized and lifestyle modifications

Conditional recommendation because of lack of anti-fracture efficacy of calcium and vitamin D in children but limited harms


Children between 4 and 17 years of age with an osteoporotic fracture who are continuing treatment with glucocorticoids at a dose of 0.1 mg/kg/day or greater for 3 months or more:

  • Treat with an oral bisphosphonate (IV bisphosphonate if oral treatment contraindicated) plus calcium and vitamin D over treatment with calcium and vitamin D alone.

Conditional recommendation because of very low-quality anti-fracture data in children but moderate-quality evidence of low harms of oral bisphosphonates in children and less potential harm of oral over IV bisphosphonates



Glucocorticoid-induced osteoporosis treatment guidelines - Recommendations for follow-up treatment for prevention of Glucocorticoid-induced Osteoporosis:

Adults 40 years of age or older who continue using Glucocorticoid treatment and who have any of the following:​​​​​​​​​​​​​​

  • who had a fracture that occurred after oral bisphosphonate therapy for 18 months or more
  • who have had a significant loss of bone mineral density of 10%/year or more
  • Treat with another class of osteoporosis medication like teriparatide or denosumab or
  • consider Intravenous bisphosphonate (if poor medication or adherence) with calcium and vitamin D over calcium and vitamin D alone or over calcium and vitamin D and continued oral bisphosphonate.

Conditional recommendation (very low-quality evidence)


Adults aged 40 years or more who have completed 5 years of oral bisphosphonate treatment and who continue GC treatment and are assessed to be at moderate-to-high risk of fracture

  • Continue treatment with an oral bisphosphonate beyond 5 years or
  • switch to intravenous bisphosphonate (if poor adherence or absorption) or
  • switch to another class of an OP treatment over calcium and vitamin D alone.

Conditional recommendation

Very low-quality data are available on the benefits and harms in GC-treated patients.

Moderate-quality data regarding the continuation of OP medication after 5 years in high-risk patients. 


Adults age 40 years or more taking an osteoporosis medication in addition to calcium and vitamin D who discontinue glucocorticoid treatment and are assessed to be at low risk of fracture

  • Discontinue the treatment but continue calcium and vitamin D over continuing the osteoporosis medication.

conditional recommendation (evidence is very low quality and too indirect for the population)


Adults aged 40 years or more taking an osteoporosis medication in addition to calcium and vitamin D who discontinue glucocorticoid treatment and are assessed to be at moderate-to-high risk of fracture

  • Complete the osteoporosis treatment rather than discontinuing it.

Strong recommendation for high-risk patients 

Conditional recommendation (because of lower fracture risk compared to potential harms for moderate-risk patients)

  The updated osteoporosis treatment guidelines presented here may not be applicable to glucocorticoid-treated patients with multiple risk factors or feasible for patients with financial or social barriers to testing and treatment.

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