Denosumab Over Alendronate for Women with RA?

December 8, 2016

Women who have rheumatoid arthritis might benefit from treatment with denosumab over alendronate. According to a new study, denosumab is more effective at bone healing.

Women who have rheumatoid arthritis might benefit from treatment with denosumab over alendronate. According to a new study, denosumab is more effective at bone healing.

Rheumatoid arthritis patients receiving denosumab treatment experience partial repair of bone erosion. To make this happen, denosumab inhibits the receptor activator of nuclear factor kappa B ligand. In contrast, erosions continued to worsen for patients taking alendronate.

Nuclear factor kappa B ligand (RANKL) is responsible for the mediation of bone resorption. Denosumab works by binding to RANKL and inhibiting its activity. It’s also been shown to inhibit bone erosion progression and reduce bone loss symptoms when compared to a placebo or other disease modifying anti-rheumatic drugs (DMARDs).

The study, published in Arthritis Care & Research, is significant for two reasons. It is the first publication to reveal a single 60 mg dose of denosumab can create partial bone erosion repair in rheumatoid arthritis patients. And, it also provides evidence supporting denosumab as a new, safe therapy that protects against bone-destructive disease while increasing the likelihood of pre-existing erosion healing.

Using data from a randomized-controlled trial, researchers led by Lai-Shan Tam, M.D., from The Prince of Wales Hospital in Hong Kong, conducted a post-hoc analysis. Investigators randomized 40 patients, over age 18, in a 1:1 radio to receive with a 60 mg subcutaneous denosumab dose or 70 mg oral alendronate doses weekly for six months.

To monitor progress, they measured the size of individual bone erosions and the presence and extent of erosion-associated sclerosis in the second metacarpal head in patients’ non-dominant hands. Measurements were taken at baseline, three months, and six months. At each assessment, researchers also analyzed 28 joints for tenderness, swelling, and C-reactive protein.

According to study results, researchers noticed 42 erosions at baseline. They also noted differences between denosumab and alendronate at six months. With denosumab, the width, depth and volume of erosions was significantly lower: -0.23mm, -0.16mm, and -0.91mm3, respectively, with all p<0.01. In the alendronate group, parameters increased for width, depth, and volume: 0.19mm, 0.32mm, 1.38mm3, respectively, with p<0.01. For all group differences p<0.01.

Data analysis also showed the erosion margin’s bone mineral density increased significantly only after denosumab treatment. Denosumab measurements showed 1.975mg/cm3, p<0.005. Alendronate measurements revealed -5.44mg/cm3, p=0.51. The different between groups was p<0.05.

“Alendronate has to be internalized into the bone substance to act upon osteoclasts, whereas denosumab, being a circulating antibody, can act in the extracelluar milieu,” researchers wrote. “Denosumab seems to have a wide distribution of action than alendronate, potentially affecting any site of osteoclastic activity.”

Investigators used HR-pQCT to capture detailed analysis of bone structures, particularly bone erosions. Acquiring data to this degree provides insight into erosion depth and width, as well as erosion repair.

In addition, this study did not check bone turnover markers. Additional studies should investigate whether bone markers might be useful in predicting erosion repair in rheumatoid arthritis patients.

Lastly, the study population was a small one with long-standing disease. It didn’t allow for enough patient stratification.

Takeaways

  • This is the first study the present denosumab as a safe, effective therapy against bone destruction while promoting bone healing.
  • At six months, a single dose of denosumab led to greater inhibition of bone erosion and greater healing of existing bone degradation.
  • Additional research is needed to study whether patients experience a rebound effect after ceasing denosumab therapy.

 

References:

Lai-Shan Tam, M.D., “Repair of bone erosion in rheumatoid arthritis by denosumab: a high-resolution peripheral quantitative computed tomography study,” Arthritis Care & Research. Published October 21, 2016. doi: 10.1002/acr.23122.