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The Effect of Intra-articular Injection of Betamethasone Acetate/Betamethasone Sodium Phosphate at the Knee Joint on the Hypothalamic-Pituitary-Adrenal Axis
  1. George Habib, MD, MPH*,
  2. Suheil Artul, MD,
  3. Mark Chernin, MD,
  4. Geries Hakim, MD§,
  5. Adel Jabbour, PhD
  1. From the *Rheumatology Clinic, Nazareth Hospital, Nazareth; and Department of Medicine, Carmel Medical Center, Haifa; †Department of Radiology, Nazareth Hospital, Nazareth; ‡Department of Medicine, Carmel Medical Center, Haifa; §Department of Orthopedics, and ||Central Laboratory, Nazareth Hospital, Nazareth, Israel.
  1. Received May 18, 2013, and in revised form July 7, 2013.
  2. Accepted for publication July 16, 2013.
  3. Reprints: George Habib, MD, MPH, Rheumatology Clinic, Nazareth Hospital, Nazareth 16000, Israel. E-mail: gshabib{at}
  4. No funding was received for this work.
  5. The authors have no disclosures to report.

A Case-Controlled Study


Background Intra-articular corticosteroid injection (IACI) of betamethasone depot preparation is a popular procedure at the knee joint. Intra-articular corticosteroid injection in general could be associated with systemic effects including suppression of the hypothalamic-pituitary-adrenal axis. There are nearly no reports on the effect of IACI of betamethasone at the knee joint on the hypothalamic-pituitary-adrenal axis.

Method Consecutive patients attending the rheumatology or orthopedic clinic with osteoarthritic knee pain who were not responding satisfactorily to medical and physical therapy were allocated to group 1 after consent and given IACI of 6 mg of betamethasone acetate/betamethasone sodium phosphate. After completion of this part, consecutive age- and sex-matched patients were allocated to group 2 and given intra-articular injection of 60 mg of sodium hyaluronate. Demographic, clinical, laboratory, and radiographic variables were documented. Just before the knee injection and 1, 2, 3, 4, and 8 weeks later, patients had 1-μg adrenocorticotropin hormone (ACTH) stimulation test. Secondary adrenal insufficiency (SAI) was defined as levels of less than 18 µg/dL and lack of a rise of more than 6 µg/dL in serum cortisol level, 30 minutes after the ACTH stimulation test.

Patients were blinded to the injected material, and all injections were ultrasound guided.

Results Twenty patients were enrolled in each group and equally divided between the 2 sexes. The mean age of the patients was approximately 54 years in both groups. No significant difference in any variable was seen between the 2 groups. One patient only from group 1 (the betamethasone group) had SAI 3 weeks after the IACI compared to none in the control group (P > 0.9999). His serum cortisol level 30 minutes after the ACTH stimulation was 17 µg/dL, with a rise of 3 µg/dL from baseline.

Conclusion Intra-articular corticosteroid injection of 6 mg of betamethasone acetate/betamethasone sodium phosphate at the knee joint was not significantly associated with SAI at the time points tested.

Key Words
  • intra-articular corticosteroid injection
  • betamethasone
  • osteoarthritis of the knee
  • hypothalamic-pituitary-adrenal axis
  • secondary adrenal insufficiency

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