Prolia Approved for Treatment of Steroid Induced Osteoporosis
by Dr. David Borenstein, MD & Dr. C.H. Weaver M.D. updated 5/2019
Corticosteroids (Deltasone, Depo-Medrol, for example) are a mainstay of therapy for a wide variety of medical conditions, including asthma, rheumatoid arthritis, and ulcerative colitis. Many individuals require corticosteroids for extended periods of time at extra-physiologic doses (greater than 7.5 mg per day). While corticosteroids are necessary for a number of illnesses, this hormone is associated with a wide range of side effects including loss of bone mineral density resulting in osteopenia or osteoporosis. Bone loss may start within a few months of starting corticosteroids. Both of these deficiencies of bone density may result in atraumatic fractures.
Denosumab (Prolia) is an antibody against RANK-ligand, a protein that signals osteoclasts (bone disintegrating cells) to turn on. Blocking this signal allows osteoblasts (bone-forming cells) to build bone with less hindrance. The FDA has approved Denosumab for the treatment of osteoporosis that occurs related to growing older. A recent phase 3 trial reported by Amgen has resulted in the FDA approving Denosumab for the treatment of glucocorticoid-induced osteoporosis (GIOP).
In this study of 795 patients receiving glucocorticoid treatment of greater than or equal to 7.5 mg/day of oral prednisone for a duration of 6 months or longer, were treated with Denosumab 60 mg subcutaneously every 6 months or Risedronate 5mg orally daily. Denosumab demonstrated a significantly greater increase in lumbar spine BMD compared to risedronate at one year (3.8% versus 0.8%, respectively).
Denosumab therapy is usually prescribed to older individuals with post-menopausal osteoporosis. The approval of Denosumab for GIOP allows for the use of the antibody for pre-menopausal women and adult men of any age who are at risk because of the prolonged use of corticosteroids.
Prolia Superior to Actonel for Steroid Caused Osteoporosis
A 60 mg dose of subcutaneous Prolia administered every 6 months for 24 months was superior to once daily oral Actonel (risedronate) for increasing hip and spine bone mineral density (BMD) for patients with glucocorticoid-induced osteoporosis. This clinical trial directly compared subcutaneous
Prolia administered once every 6 months with once-daily oral Actonel in 795 patients. Participants were men and women at least 18 years of age who had been receiving at least 7.5 mg of prednisone or equivalent daily for less than 3 months (glucocorticoid-initiating group) or for 3 months or more (glucocorticoid-continuing group). Participants were randomly assigned to Prolia or Actonel for 24 months, with daily vitamin D and calcium.
At 24 months and every time point assessed, Prolia was shown to be superior to Actonel for increasing lumbar spine and total hip Bone Mineral Density (BMD) in both glucocorticoid-initiating participants and glucocorticoid-continuing participants. The development of side effects, and fractures were similar with both treatments.
The doctors concluded that Prolia was superior to risedronate with a similar safety profile, and that Prolia represents a new and effective treatment option for glucocorticoid-treated patients with osteoporosis.
Saag KG, Pannacciulli N, Geusens P, et al. Denosumab vs risedronate in glucocorticoid-induced osteoporosis: final results of a 24-month randomized, double-blind, double-dummy trial [published online February 28, 2019]. Arthritis Rheumatol. doi:10.1002/art.40874