Romosozumab Treatment in Postmenopausal Women with Osteoporosis

Garrett Brown, Mercer University College of Pharmacy

According to the Centers for Disease Control and Prevention, the incidence of osteoporosis of lumbar spine or femoral neck in women is 16%. [1]  Fractures are reported to be the most serious complication from osteoporosis, and result in increased mortality and morbidity.  [2]

Fewer than 25% of patients are reported to have received pharmacologic treatment for osteoporosis after a fracture.  [3]

Romosozumab (AMG 785) is a monoclonal antibody that has been shown to increase bone formation and decrease bone resorption.  It is suggested that these effects occur due to the drug binding and inhibiting sclerostin.  Sclerostin is a protein that is secreted by bone cells and has been shown to inhibit bone formation in the body.  [4]


 

Romosozumab Treatment in Postmenopausal Women with Osteoporosis [5]

Design International, randomized, double-blinded, placebo-controlled, parallel-group; N= 7,180
Objective To evaluate the effects of one year of romosozumab treatment on the risk of bone fracture
Study Groups Romosozumab (n= 3,589); placebo (n= 3,591)
Methods Women were randomly assigned, in a 1:1 ratio, to receive subcutaneous injections of 210 mg of romosozumab or placebo once monthly for 12 months during the double-blind phase of the trial. Patients then received open-label denosumab, administered subcutaneously at a dose of 60 mg every 6 months, for an additional 12 months; the initial group assignment was still blinded.
Duration March 15th, 2012 – December 14th, 2015
Primary Outcome Measure Cumulative incidences of new vertebral fracture at 12 months and at 24 months
Baseline Characteristics
Rosomozumab Placebo
Average age (yrs) 70.8 70.9
Age ≥ 75, n (%) 1,121 (31.2) 1,119 (31.2)
Hispanic, n (%) 1,416 (39.4) 1,427 (39.8)
Non-Hispanic, n (%) 2,175 (60.6) 2,162 (60.2)
Average Bone Density T-score
Lumbar spine -2.71 -2.72
Total hip -2.46 -2.48
Femoral neck -2.74 -2.76
Prevalent vertebral fracture, n (%) 645 (18) 672 (18.7)
Non-vertebral fracture ≥ age 45, n (%) 782 (21.8) 778 (21.7)
Average FRAX score 13.4 13.4
Results
Romosozumab Placebo Risk ratio:

(95 % Confidence Interval (CI))

p-value
New vertebral fracture at 12 months, n (%) 16 (0.5) 59 (1.8) 0.27 (0.16-0.47) p< 0.001
Non-vertebral fracture at 12 months, n (%) 56 (1.6) 75 (2.1) 0.75 (0.53-1.05) p= 0.10
Romosozumab 12 months then denosumab 12 months Placebo 12 months then denosumab 12 months Risk Ratio 95% CI p-value
Cumulative vertebral fracture at 24 months, n (%) 21 (0.6) 84 (2.5) 0.25 (0.16-0.40) p< 0.001
Cumulative non-vertebral fracture at 24 months, n (%) 96 (2.7) 129 (3.6) 0.75 (0.57-0.97) p= 0.06
Adverse Events Common Adverse Events: back pain (11%), arthralgia (14%), injection site pain (2%)
Serious Adverse Events: death: romosozumab (0.8%); cardiovascular event: romosozumab (1.2%)
Percentage that Discontinued due to Adverse Events: Not reported
Study Author Conclusions Romosozumab increases bone formation and decreases bone resorption. At one year of romosozumab treatment, there was a lower risk of vertebral and clinical fractures than the risk with placebo.

 

The patient population of this study contained a large percentage of Latin Americans. Due to this fact, it is difficult to draw generalized conclusions that apply the data to all populations, as only 90 participants were from the United States.  Another limitation was the exclusion of patients with a history of hip fracture, which may represent a patient population that is in great need of a drug like romosozumab.

 

Strengths of the study include the large patient population, the inclusion of many patients with age ≥ 75 years old, and that the study was double-blinded during the first phase.

 

While the 12 and 24 month data for romosozumab was statistically beneficial over placebo, it would also be clinically significant because of its safety profile.  Further head-to-head studies against bisphosphonates would provide more evidence for romosozumab’s use in osteoporosis.

 

References

  1. Center for Disease Control and Prevention. http://www.cdc.gov/nchs/fastats/osteoporosis.htm. Accessed on September 29, 2016.
  2. Cummings SR, Melton LJ. Epidemiology and outcomes of osteoporotic fractures. Lancet 2002;359:1761-1767
  3. Harrington JT, Broy SB, Derosa AM, Licata AA, Shewmon DA. Hip fracture patients are not treated for osteoporosis: a call to action. Arthritis Rheum 2002;47:651-654
  4. Padhi D, Jang G, Stouch B, Fang L, Posvar E. Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res 2011;26:19-26
  5. Cosman F, Crittenden DB, Adachi JD, et al. Romosozumab Treatment in Postmenopausal Women with Osteoporosis. N Engl J Med. 2016;

 

 

 

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