8.2 Drug-Induced Bone Loss & Glucocorticoid-Induced Osteoporosis
Key Takeaways
ACR assessment applies to adults receiving systemic glucocorticoids at ≥2.5 mg/day prednisone equivalent for more than three months. At age 40 or older, include FRAX in the applicable population.
For daily doses above 7.5 mg prednisone equivalent, the ACR FRAX multipliers are 1.15 for major osteoporotic fracture and 1.20 for hip fracture.
An osteoporotic fracture can establish ACR very high risk even with a T-score in the low bone mass range.
Use the product-specific indication and the patient’s risk, comorbidities and treatment history to select therapy.
Assess systemic glucocorticoid exposure early
Systemic glucocorticoids suppress bone formation and can increase resorption early in treatment. Bone loss and fracture risk can rise soon after exposure. The daily dose, duration, cumulative exposure, underlying illness and prior fracture all matter. A vertebral fracture can occur before the DXA T-score reaches the osteoporosis range. No single T-score range identifies a glucocorticoid-related fracture.
The 2022 American College of Rheumatology (ACR) guideline addresses adults beginning or continuing systemic glucocorticoids at at least 2.5 mg/day prednisone equivalent for more than three months. Assess clinical risk and obtain DXA with vertebral fracture assessment or spine radiographs as soon as possible. The guideline discusses initial assessment within six months of starting therapy. Use FRAX in the applicable population aged 40 or older. Below 40, rely on clinical assessment, DXA and vertebral imaging. FRAX is not validated for that younger group. These are ACR assessment recommendations. The ISCD adult VFA case-finding rule serves a different purpose and uses a T-score below −1.0 plus an eligible trigger.
Assign risk using the applicable criteria
For adults aged 40 or older, the ACR uses fracture history, BMD, adjusted FRAX probabilities and glucocorticoid exposure to identify the highest applicable risk category. The table gives the key decisions, with major osteoporotic fracture abbreviated as MOF.
| Risk tier | How to recognize it in an adult aged 40 or older |
|---|---|
| Very high | Prior osteoporotic fracture, T-score at or below −3.5, adjusted MOF at least 30% or hip at least 4.5%, at least 30 mg/day for more than 30 days, or at least 5 g in a year. |
| High | In the absence of a very-high-risk feature, T-score at or below −2.5 and above −3.5, adjusted MOF from 20% to below 30%, or adjusted hip from 3% to below 4.5%. |
| Moderate | The ACR table includes MOF from 10% to below 20%, hip probability above 1% and below 3%, or a T-score in its −1.0 to −2.4 band. Use the full assessment rather than classifying from a single rounded risk estimate. |
| Low | The ACR table lists MOF below 10%, hip below 1% and a T-score above −1.0 in the absence of a higher-risk feature. |
For doses above 7.5 mg/day, ACR uses relative multipliers of 1.15 for MOF and 1.20 for hip. See FRAX limitations and adjustments for the calculation. ACR uses separate criteria below age 40. For example, a prior osteoporotic fracture or very high glucocorticoid exposure can identify very high risk. Continuing at least 7.5 mg/day for at least six months with a Z-score below −3 is one moderate-risk pattern. Interpret serial change and other features using the age-specific criteria.
A 59-year-old on 20 mg/day of prednisone develops a low-trauma T8 fracture during a planned six-month course. Her valid spine T-score is −1.7. The prior osteoporotic fracture puts her in the ACR very-high-risk category. Waiting for a lower score would miss a risk criterion already present.
Keep recommendations and product labels separate
Optimize age-appropriate calcium and vitamin D intake and address activity, tobacco, alcohol and falls. ACR supports pharmacologic treatment at elevated risk. In adults aged 40 or older at high or very high risk, it strongly recommends osteoporosis medication over no treatment and oral bisphosphonates over no treatment. It conditionally favors PTH/PTHrP therapy over antiresorptives at very high risk. In one randomized GIOP trial, teriparatide produced fewer new vertebral fractures than alendronate at 36 months. Match the choice to the individual and the current product label. For example, the U.S. Prolia GIOP indication is for high-risk men or women on at least 7.5 mg/day prednisone equivalent expected to continue systemic treatment at least six months. That indication is different from the ACR assessment entry criterion.
ACR recommends fracture risk reassessment every one to two years for adults continuing at least 2.5 mg/day who have moderate, high or very high risk and are continuing osteoporosis therapy for at least a year. The guideline also gives one- to two-year reassessment for specified adults on lower-dose chronic glucocorticoids who are not taking osteoporosis medication. Annual BMD assessment can be preferred until stability in very-high-risk patients. Use serial BMD and the clinical review to assess response. FRAX has not been validated for that purpose. A scheduled scan cannot replace earlier clinical review for a new fracture. Document dose and duration changes and the treatment transition plan, especially if denosumab is stopped.
Recognize other medication-associated risks
- Antiseizure medication. Phenytoin induces hepatic enzymes that can increase vitamin D metabolism. In a patient on long-term phenytoin with low 25-hydroxyvitamin D, low calcium and elevated PTH, the medicine may contribute. Consider other causes and clinical context before attributing the pattern or changing therapy.
- Proton pump inhibitors. The omeprazole label notes an association between long-term or multiple-daily-dose treatment and fracture. This association cannot diagnose an individual calcium absorption problem.
- Depot medroxyprogesterone acetate. The U.S. contraceptive injection label warns about duration-related BMD loss that may not fully reverse. Use beyond two years is generally discouraged unless alternatives are inadequate. Cancer-treatment exposures require separate assessment.
ACR GIOP guideline · ISCD Adult Official Positions · Oral glucocorticoid cohort · GIOP randomized trial · Prolia label · Dilantin label · Omeprazole label · Depo-Provera CI label
A 59-year-old woman taking prednisone 20 mg/day develops a low-trauma T8 fracture during a planned six-month course. Her valid lumbar spine T-score is −1.7. Which ACR risk conclusion is supported?
She is at low risk because the spine T-score is above −2.5.
She can be classified only after six months of treatment.
She is at moderate risk based solely on the spine T-score.
The osteoporotic vertebral fracture places her at very high risk.
A 42-year-old patient plans to take prednisone 5 mg/day for six months. Which assessment follows the ACR guideline?
Assess clinical risk, including FRAX, and arrange DXA with VFA or spine radiographs as soon as possible.
Wait for the dose to rise above 7.5 mg/day before assessing fracture risk.
Start Prolia immediately because the patient meets its labeled glucocorticoid dose criterion.
Use FRAX alone because the result replaces the baseline imaging assessment.
A patient taking phenytoin long term has low 25-hydroxyvitamin D, low calcium and elevated PTH. Which interpretation is supported?
The calcium and PTH results establish hypercalcemic primary hyperparathyroidism.
Phenytoin-induced enzyme activity may contribute to altered vitamin D metabolism. Evaluate other contributors as well.
The results establish that phenytoin must be stopped immediately.
The 25-hydroxyvitamin D level is irrelevant because phenytoin lowers only the active metabolite.
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