Not ready for prime time
Denosumab can be effective against osteoporosis caused by transfusion-dependent thalassemia (TDT), according to new research.
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The study authors found that patients who received twice-yearly injections of denosumab experienced a significant increase in bone density and reduction in bone pain. Their findings were published in Blood Advances.
“Not only is denosumab associated with improved bone health and reduced pain, but its ease of administration may very well make this drug superior to bisphosphonates for the treatment of osteoporosis in patients with TDT and osteoporosis,” senior study author Evangelos Terpos, MD, of the National and Kapodistrian University of Athens, said in a statement.
For this phase 2b study, Dr. Terpos and his colleagues evaluated 63 patients with TDT and osteoporosis, randomized to receive 60 mg of denosumab (n = 32) or placebo (n = 31) on days 0 and 180 of a 12-month period. Patients in both arms also received daily supplements of calcium and vitamin D.
Baseline characteristics were largely similar between the treatment arms. However, the mean value of bone-specific alkaline phosphatase (bALP) was significantly lower in the placebo arm than the denosumab arm – 68.48 IU/L versus 85.45 IU/L (P = .013). And the mean value of the tartrate-resistant acid phosphatase isoform–5b (TRACP-5b) marker was significantly higher in the denosumab arm than in the placebo arm – 0.42 IU/L versus 0.16 IU/L (P = .026).
The researchers measured bone mineral density in the L1-L4 lumbar spine, wrist, and femoral neck. At 12 months, the mean increase in L1-L4 bone mineral density was 5.92% in the denosumab arm and 2.92% in the placebo arm (P = .043). The mean decrease in wrist bone mineral density was –0.26% and –3.92%, respectively (P = .035).
Femoral neck bone mineral density was increased in the denosumab arm (4.08%), compared with the placebo arm (1.96%), but the difference between the two groups was not statistically significant.
Patients in the denosumab arm had a significant reduction in bone pain at 12 months, according to the McGill-Melzack scoring system and the Huskisson visual analog scale (P less than .001 for both). There was no significant change in pain for patients in the placebo arm on either scale.
At 12 months, patients in the denosumab arm had experienced a significant reduction from baseline in several markers of bone remodeling, including soluble receptor activator of nuclear factor–kappa B ligand (sRANKL), osteoprotegerin (OPG), sRANKL/OPG ratio, C-terminal telopeptide of type I collagen (CTx), TRACP-5b, and bALP.
There were no significant changes in dickkopf-1, sclerostin, or osteocalcin in the denosumab arm.
In the placebo arm, patients had a significant increase from baseline in several markers of bone remodeling, including sRANKL, OPG, dickkopf-1, sclerostin, CTx, TRACP-5b, and bALP. There was no significant change from baseline in the sRANKL/OPG ratio or osteocalcin.
In all, there were 17 adverse events in 14 patients. There were three serious adverse events in the denosumab arm – pleural effusion (grade 3), atrial fibrillation (grade 3), and supraventricular tachycardia (grade 4). All three of these adverse events were considered unrelated to denosumab.
The study was funded by Amgen, which markets denosumab. The authors reported that they had no competing financial interests.
SOURCE: Terpos E et al. Blood Adv. 2018;2:2837-47.