Glucocorticoid Use May Result in Loss of Bone Mineral Density

ACR CONVERGENCE 2022—In the GLORIA (Glucocorticoid Low-Dose in Rheumatoid Arthritis) study, Boers et al. reported that the addition of low-dose prednisolone had beneficial long-term effects in elderly patients with established rheumatoid arthritis (RA). The researchers also reported a trade-off: a 24% increase in mostly non-severe adverse events.¹ These results have sparked debate about the benefits of glucocorticoid use in older patients with inflammatory diseases, including the effects on fracture risk.

During ACR Convergence 2022, Giovanni Adami, MD, a rheumatologist at the University of Verona, Italy, presented findings from a longitudinal cohort study examining the effect of low-dose glucocorticoids on fracture risk in women with inflammatory rheumatic musculoskeletal diseases. These conditions included RA, systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), systemic sclerosis and other rheumatic diseases, such as vasculitides, polymyalgia rheumatica, spondyloarthritis and others, which were pooled.²

Methods: The researchers converted patient glucocorticoid intake to equivalent doses of prednisone, even if the glucocorticoid taken was not prednisone. The doses were recorded as 0 to 2.5 mg of daily prednisone equivalent mean dose, 2.5 mg to 5 mg of prednisone equivalent mean dose or ≥5 mg of daily prednisone equivalent mean dose. Bone mineral density (BMD) and fracture were prospectively assessed and compared with a 2:1 propensity score matched cohort of healthy women, which included data on age, T-score and the percentage of 10-year fracture risk. Kaplan-Meier curves with log-rank test were made for inflammatory rheumatic musculoskeletal diseases, which were stratified for glucocorticoid use and dosage, and matched cohort, respectively. Multivariable Cox regression survival models were also used to analyze the effect of glucocorticoids on fracture.

The Results

Over six years, 884 women (Note: ages not defined), mostly with RA, and 1,766 controls were evaluated. BMD levels decreased significantly in women who used glucocorticoids and were not receiving anti-osteoporosis treatment (Note: specific agents and routes not defined).

Patients who received the equivalent of at least 5 mg/day of prednisone had a change in BMD of -4.26% (P=0.001), with 21 fractures identified. Patients who received the equivalent of 2.5–5 mg/day of prednisone had a change in BMD of -4.23% (P=0.0422), with 12 fractures identified. Finally, patients who received the equivalent of 0–2.5 mg/day of prednisone had a change in BMD was -2.66% (P=0.0006), with 29 fractures identified. The use of anti-osteoporotic treatment increased the BMD to a greater extent in patients receiving the equivalent of less than 5 mg of prednisone daily.

The corresponding crude fracture rates were 4.8 fractures per 100 person-years for the women who received the equivalent of at least 5 mg of prednisone daily, 2.8 fractures per 100 person-years for the woman who received the equivalent of 2.5–5 mg of prednisone daily and 2.5 fractures per 100 person-years for women who received the equivalent of 0–2.5 mg of prednisone daily.

Overall, 103 fractures were registered in the propensity score matched cohort, with a crude fracture rate of 2.2 fractures per 100 person-years. Women with inflammatory rheumatic musculoskeletal diseases had a higher incidence of fracture compared with the controls. Woman who received the equivalent of at least 5 mg of prednisone daily had a two-fold higher risk of fragility fracture compared with all the other prednisone equivalent doses evaluated and the control patients (aHR 2.37, 95% CI 1.33-4.23).

In this study, doses of as low as the equivalent of 2.5 mg of prednisone daily were associated with BMD loss in women with inflammatory rheumatic musculoskeletal diseases. However, this adverse effect may be at least partially offset by the use of anti-osteoporotic drugs. The findings of this study may support the use of anti-osteoporotic treatment initiation in patients taking very low-dose prednisone, which appears to contrast to the 2022 ACR Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis.³ Further study evaluating the delineation of agents, doses, durations of treatment, patient age and risk factors, and anti-osteoporotic treatment is needed before definitive conclusions are made regarding the most recent guideline.

Michele B. Kaufman, PharmD, BCGP, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.

References

1. Boers M, Hartman L, Opris-Belinski D, et al. Low dose, add-on prednisolone in patients with rheumatoid arthritis aged 65+: The pragmatic randomised, double-blind placebo-controlled GLORIA trial. Ann Rheum Dis. 2022 Jul;81(7):925–936.
2. Adami G, Fassio A, Bertelle D, Benini C, Gatti D, Rossini M. Impact of glucocorticoid dosing and anti-osteoporotic treatment on bone health in patients with inflammatory rheumatic musculoskeletal diseases: A longitudinal cohort study [abstract L01]. Arthritis Rheumatol. 2022 Oct; 74(suppl 9).
3. 2022 American College of Rheumatology guideline for the prevention and treatment of glucocorticoid-induced osteoporosis. American College of Rheumatology. 2022 Nov 9.