In a randomized controlled study, we investigated the effect of treatment with intravenous neridronate in prepubertal children with OI. Our study suggests that quarterly intravenous infusions of the bisphosphonate significantly raise the rate of increase in BMD at both the spine and hip, the projected area of the lumbar vertebrae, and height. These results are associated with a significant decrease in the risk of clinical fractures.Introduction: Osteogenesis imperfecta (OI) is a heritable disease of connective tissue, characterized by increased bone fragility. Bisphosphonates currently seem to be the most promising therapy, but randomized, controlled studies are scarce and have never been carried out in prepubertal children. Materials and Methods:This was a randomized, controlled 3-year clinical trial. The Italian Patients' Society of OI (AsItOI) sent their members affected by any type of OI to two centers at the University of Verona (Italy) to participate in the study. Sixty-four children, 6-11 years of age for boys and 6-9 years of age for girls, with no signs of puberty and who were never treated with bisphosphonates, were randomized to either intravenous neridronate (2 mg/kg infused IV in 30 minutes every 3 months) or no treatment, with a ratio of 2:1. Control patients were given the same bisphosphonate therapy at the end of the first year. BMD and projected bone areas, as measured by DXA, at spine and hip, height, and peripheral fracture incidence, both prospective and retrospective (2 years preceding randomization), were the main outcomes of the study. Results: At the end of the first year, spine and hip BMD rose by 3.5-5.7% in control patients and by 18-25% (p < 0.001 versus controls) in the active group, respectively. During the following 2 years, the treatment in all patients was associated with BMD increases of 10-25% per year. Height and the DXA-derived projected area of lumbar spine rose during the first year of observation significantly more in the active group than in the control group (<0.01 and <0.05, respectively). Both height and spine projected area continued to rise in the treated patients toward levels found in healthy individuals. During the first year of treatment, 45% of the control patients and 27% of the active group had a nonvertebral fracture, but this difference was not statistically significant (p ‫ס‬ 0.2). The total number of fractures was 18 in the 22 control patients and 13 in the active group (relative risk, 0.36; 95% CI, 0.15-0.87; p < 0.05). Conclusion: Intravenous neridronate infusions, administered quarterly, significantly increase BMD and lower the risk of clinical fracture in prepubertal children with OI.

Neridronate therapy in adult patients with OI significantly increases the cross-sectional area of the proximal radius. This observation may provide an additional explanation for the antifracture efficacy of bisphosphonates.Introduction: Bisphosphonate therapy decreases by 70-90% the fracture risk in patients with osteogenesis imperfecta (OI). This decrease is somewhat greater than that expected from the BMD changes, supporting the hypothesis that bisphosphonate therapy is associated with structural changes, not detectable by BMD measurements. Materials and Methods: To explore this hypothesis, pQCT measurements at the nondominant radius were obtained in a group of adult OI patients participating in a randomized clinical trial with neridronate. Results: The total volumetric BMD of the ultradistal radius rose significantly in patients treated with neridronate and calcium + vitamin D (neridronate group) compared with patients treated with calcium + vitamin D alone (control group). No significant differences were observed in trabecular BMD and in volumetric cortical density in either group. In the neridronate group, the cross-sectional area rose significantly versus both baseline values and the control group. These latter changes were associated with ∼20% increases in bending breaking resistance index (BBRI). Conclusion: Our observation, if extended to postmenopausal osteoporosis, may provide a new explanation for the fracture risk reduction observed in osteoporotic patients treated with bisphosphonates.

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The incidence of osteoporotic fracture in males is approximately one-third of that observed in women, but information on specific therapies is almost exclusively limited to bisphosphonate alendronate. The most important study with this compound included 241 men, randomized to receive either alendronate 10 mg/day or placebo. In another study 134 men were given either 10 mg alendronate or alfacalcidiol 1 microg/day. After 24 months, the treatment with alendronate bone mineral density (BMD) significantly increased in both studies by 7-10% at the lumbar spine and by 2.5-5.2% at the femoral neck. These changes were associated with decreases in vertebral fracture rate and in stature loss, both statistically significant when the data of the two trials were meta-analysed. The BMD changes after alendronate therapy were comparable to those observed in postmenopausal osteoporosis. This was confirmed in a trial specifically designed to compare alendronate efficacy in men and postmenopausal women with either primary or secondary osteoporosis. Gender-comparative efficacy data can also be inferred from clinical trials in glucocorticoid-induced osteoporosis of alendronate, risedronate, and etidronate, carried out in both women and men. By combining the results of all these trials, bisphosphonate efficacy in terms of both BMD changes and fracture incidence appears to be moderate in premenopausal women but quite obvious and comparable in males and postmenopausal women.