Denosumab effects on serum levels of the bone morphogenetic proteins antagonist noggin in patients with transfusion-dependent thalassemia and osteoporosis.

Abstract

INTRODUCTION:

Noggin is an antagonist of bone morphogenetic proteins (BMPs) and has a strong effect on osteogenesis. Osteoporosis is a common complication of transfusion dependent beta-thalassemia (TDT) and denosumab has been recently emerged as a promising therapeutic option. This was a post hoc investigation of serum noggin levels among TDT patients with osteoporosis who participated in a randomized, placebo-control, phase 2b study.

METHODS:

Patients received either 60 mg denosumab (n = 32) or placebo (n = 31) every 6 months for 12 months. Noggin was measured, for the first time in thalassemia patients, at baseline and at 12 months, using a recently developed high sensitivity fluorescent immunoassay.

RESULTS:

Both groups showed a significant increase in noggin serum levels (denosumab p < 0.001; placebo p < 0.0001). Interestingly, the increase was higher in the placebo group. Furthermore, we observed a strong correlation between noggin and wrist bone mineral density (r = -0.641, p = 0.002) only in the denosumab group.

CONCLUSION:

In conclusion, higher noggin levels reflected more BMP inhibition, since our assay detects free bioactive noggin, which in turn impaired bone formation in placebo group. Therefore, denosumab possibly regulates noggin and favours bone turnover in TDT patients with osteoporosis through a novel mechanism of action.

• Authors: Ersi Voskaridou, Ioannis Ntanasis-Stathopoulos, Dimitrios Christoulas, Linda Sonnleitner, Athanasios Papaefstathiou, Maria Dimopoulou, Albert Missbichler, Nikolaos Kanellias, Konstantina Repa, Athanasios Papatheodorou, Melpomeni Peppa, Gerhard Hawa, Evangelos Terpos
• Journal: Hematology (Amsterdam, Netherlands) (Hematology) Vol. 24 Issue 1 Pg. 318-324 (Dec 2019) ISSN: 1607-8454 [Electronic] England
• PMID: 30665323 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial)

Chemical References

• Carrier Proteins
• noggin protein
• Denosumab

Topics

• Adult
• Aged
• Bone Remodeling (drug effects)
• Carrier Proteins (blood)
• Denosumab (administration & dosage)
• Female
• Humans
• Male
• Middle Aged
• Osteoporosis (blood, drug therapy)
• Thalassemia (blood, drug therapy)