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Neridronic acid safe, effective in children with osteogenesis imperfecta
Children and adolescents with osteogenesis imperfecta who received IV neridronate therapy over 3 years saw gains in bone mineral density at the lumbar spine and total hip while also experiencing reductions in bone turnover markers and fracture risk, according to a study from researchers in Italy.
“Bisphosphonate therapy has been used to treat patients with [osteogenesis imperfecta] for the past 3 decades and is currently the most widely available medical treatment for [osteogenesis imperfecta], even though many different compounds, dosage and protocols have been proposed,” Luca Idolazzi, MD, assistant professor in the rheumatology unit, department of medicine at the University of Verona, Italy, and colleagues wrote. “The positive effects of bisphosphonates on areal BMD (by DXA) at the spine and other skeletal sites are widely recognized. More controversial is the question of what clinically relevant benefit children with [osteogenesis imperfecta] may have from higher areal BMD due to the fact that some clinically relevant outcomes, such as fracture rate, mobility and quality of life are difficult to assess in [osteogenesis imperfecta].”
Neridronate is an amino-bisphosphonate that is structurally similar to alendronate and pamidronate and is available in both intramuscular and IV formulations, according to study background. The therapy has been extensively investigated in patients with osteogenesis imperfecta in Italy and is the only drug licensed in the country for the treatment of osteogenesis imperfecta.
Idolazzi and colleagues analyzed data on 55 children with a diagnosis of osteogenesis imperfecta who were naive to bisphosphonate treatment (55.5% boys; mean age, 13 years). Neridronate was administered by IV infusion at a dose of 2 mg/kg (maximum dose of 100 mg) every 3 months for 3 years, along with 1,000 mg daily calcium and 800 IU daily vitamin D supplementation. Participants underwent DXA measurements to assess BMD at the lumbar spine (78.2% of patients), hip (54.5% of patients) and ultradistal and proximal radius every 6 months; serum calcium, phosphate, albumin and fasting urinary calcium to creatinine ratio were measured at baseline and every 3 months. In a proportion of patients, researchers assessed serum bone turnover markers; total and bone alkaline phosphatase were performed every 12 months. All fractures that occurred during treatment were evaluated by X-ray.
During follow-up, mean lumbar spine BMD progressively increased from baseline through month 6 (mean, 15% increase) to month 36 (mean, 51% increase) and was associated with a concomitant increase in bone mineral content and bone area, according to researchers.
“None of the patients with repeated measurements of lumber spine BMD had any lumbar vertebral fractures for the duration of the study,” the researchers wrote.
At the total hip, mean BMD for the cohort also increased from baseline at all subsequent time points, from a mean of 11% at month 6 to a mean 41% increase at month 36, and was also associated with a concomitant increase in bone mineral content and bone area, the researchers wrote. Bone turnover markers decreased from baseline levels at all subsequent time points.
Researchers did not observe a statistically significant effect on fracture risk, but there was an observed reduction in fractures for the cohort.
“In the 3 years before treatment was undertaken, 43 of the 55 patients (78.2%) incurred at least one fracture,” the researchers wrote. “Over the 3-year study period, the rate of patients with new fractures decreased to 24 of 55 (43.6%).”
The most frequently reported adverse events were arthralgia, fever and joint sprain. An acute-phase reaction was reported in 26 patients, but none led to treatment discontinuation. None of the reported serious adverse events were considered treatment-related. – by Regina Schaffer
Disclosures: Abiogen Pharma provided neridronate for this study. Idolazzi reports receiving speaking fees from AbbVie, Eli Lilly, Novartis and UCB. Please see the full study for the other authors’ relevant financial disclosures.