Postmenopausal Japanese women with osteoporosis assigned the monoclonal antibody romosozumab experienced gains in bone mineral density at the lumbar spine, total hip and femoral neck, as well as a decrease in bone resorption, particularly at the 210-mg monthly dose, according to findings published in Bone.
Hideaki Ishibashi, MD, PhD, of the department of orthopedic surgery at INA Hospital in Saitama, Japan, and colleagues analyzed data from 252 ambulatory Japanese women aged 55 to 85 years with osteoporosis, recruited from 24 centers across Japan (mean age, 68 years; mean baseline BMD T-scores were –2.7 at lumbar spine, –1.9 at total hip and –2.3 at femoral neck). Researchers randomly assigned women to one of four treatment groups: placebo or subcutaneous romosozumab (Amgen and UCB Pharma) 70 mg, 140 mg or 210 mg monthly for 12 months (n = 64 per treatment group). Dosing adjustments were not permitted. Patients in each treatment group also received daily supplementation with at least 500 mg calcium and at least 600 IU vitamin D. Patients were followed for an additional 3 months after treatment period ended. Women underwent DXA scans of the lumbar spine and proximal femur at baseline and 6 and 12 months; assessment of anti-romosozumab antibodies occurred at baseline and months 1, 3, 6, 9, 12 and 15; fasting blood samples were collected at baseline, week 1 and months 1, 2, 3, 6, 9 and 12 to measure bone turnover markers. Primary endpoint was the percentage change from baseline at 12 months in the lumbar spine, as measured by DXA.
Compared with placebo, each dose of romosozumab increased BMD at the lumbar spine at 12 months; mean percentage increases across doses of 70 mg, 140 mg and 210 mg were 8.4%, 13.3% and 16.9%, respectively, vs. a mean 0.9% increase in the placebo group (P < .001 for all vs. placebo).
At 6 months, romosozumab 210 mg increased BMD at the lumbar spine by a mean of 13.1%, compared with a mean increase of 1.2% in the placebo group (P < .001). At months 6 and 12, romosozumab 210 mg increased BMD at the total hip and femoral neck from baseline compared with placebo (P < .001 for all). Compared with romosozumab 70-mg and 140-mg doses, researchers observed the largest increase in BMD from baseline in the romosozumab 210-mg group at each site at months 6 and 12, except for femoral neck at month 12.
Researchers also observed a transient, dose-dependent increase in the bone-formation marker P1NP from baseline to month 12 in all romosozumab groups; median values for P1NP in the romosozumab groups peaked at 1 month and returned to baseline levels between months 2 and 6, depending on dose. Similar results were observed for bone-specific alkaline phosphatase and osteocalcin.
During 15 months, 74.6% of patients in the romosozumab group and 68.3% of patients in the placebo group reported adverse events; serious adverse events were reported by 5.3% of romosozumab patients and 6.3% of placebo patients. No serious adverse event was considered related to romosozumab treatment.
“Consistent with international phase 2 and phase 3 studies, romosozumab exhibited a dual effect in this study of Japanese patients by increasing bone formation and decreasing bone resorption,” the researchers wrote. “Transient increases in the bone-formation marker P1NP, combined with decreases in the bone-resorption marker CTX, supported the subsequent large increases in BMD at the spine and hip. This is consistent with increases in bone mass and strength following romosozumab administration in animal models.”
The researchers noted that the study was not powered to assess the effect of romosozumab on fractures or adverse events of fracture, and did not assess the broader safety profile of the drug, which was evaluated in an earlier study. – by Regina Schaffer
Disclosures: Amgen and UCB Pharma sponsored this study and contributed to the study design and collection, analysis and interpretation of data. Ishibashi reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.