Bisphosphonate Treatment and the Characteristics of Femoral Fractures in Children With Osteogenesis Imperfecta.

Context: The short-term benefits of bisphosphonates (BPs) are evident in the treatment of children with osteogenesis imperfecta (OI), but some concerns related to long-term effects remain. Objective: To elucidate the effect of BPs on characteristics of femoral fractures in children with OI. Design and Setting: Retrospective cohort study at a university hospital. Patients and Main Outcome Measure: The study included 93 patients with OI. We recorded fracture histories and analyzed all femoral fractures for location and fracture type using radiographs obtained at fracture diagnosis. Effects of BPs were evaluated by comparing fracture characteristics in three groups: patients (1) naive to BPs, (2) receiving ongoing BP treatment, and (3) whose treatment was discontinued. Results: In total, 127 femoral fractures occurred in 24 patients. Of the fractures, 63 (50%) occurred in patients naive to BPs, 44 (35%) during BP treatment, and 20 (16%) after treatment discontinuation. Mid or distal shaft fractures were most common (41%), followed by subtrochanteric (33%) and distal (20%) fractures. Almost all fractures were transverse (65%) or oblique (28%). The pattern of femoral fractures was similar in all three BP treatment groups (P = 0.78 for location; P = 0.35 for fracture type) and was not related to cumulative BP dose. Instead, OI type correlated with fracture characteristics, and distal location and transverse configuration were more common in the more severe types III and IV compared with type I OI. Conclusion: Characteristics of femoral fractures in children with OI are affected by OI type but not by BP exposure.

Timing of dental development in osteogenesis imperfecta patients with and without bisphosphonate treatment.

Bisphosphonates have established their role as medical therapy for pediatric osteogenesis imperfecta (OI) patients. Since bisphosphonates have also been shown to delay tooth development in animal models, we aimed to assess whether the medication has a similar effect on children with OI. In this cross-sectional study, bisphosphonate-treated OI patients of whom dental panoramic tomograph was taken between 3 and 16years of age formed the study group. The patients, 22 in total, had been treated with pamidronate, zoledronic acid or risedronate for at least one year before the radiography. Developmental stage of the permanent teeth, resorption of the deciduous teeth, and number of the erupted permanent teeth were radiographically assessed in the left mandibular quadrant. Dental panoramic tomographs of 50 OI patients, naïve to bisphosphonates, and of 50 healthy individuals of the same age were used as controls. The dental development was statistically significantly accelerated in the OI group naïve to bisphosphonates showing median advancement of dental age by 0.63years from chronological age and median increase in the number of erupted teeth by 0.31 as compared to Finnish norms. Bisphosphonate-treated OI patients displayed, however, age-appropriate dental development. The OI patients not treated with bisphosphonates also showed statistically significantly faster resorption of the deciduous teeth than the treated ones, and displayed an altered interrelationship between the resorption stage of an individual primary tooth and the developmental stage of the succedaneous permanent tooth, unlike the OI patients treated with bisphosphonate. No correlation between either cumulative bisphosphonate dose or between treatment length and any measured component of the dental development was found. To conclude, OI itself was found to lead to advanced dental development. Bisphosphonate treatment had a delaying effect in all the three aspects studied, resulting in a rate of dental development indistinguishable from normal.

Cranial base pathology in pediatric osteogenesis imperfecta patients treated with bisphosphonates.

OBJECT: Cranial base pathology is a serious complication of osteogenesis imperfecta (OI). Our aim was to analyze whether bisphosphonate treatment, used to improve bone strength, could also prevent the development of craniocervical junction pathology (basilar impression, basilar invagination, or platybasia) in children with OI. METHODS: In this single-center retrospective study the authors analyzed the skull base morphology from lateral skull radiographs and midsagittal MR images (total of 94 images), obtained between the ages of 0 and 25 years in 39 bisphosphonate-treated OI patients. The results were compared with age-matched normative values and with findings in 70 OI patients who were not treated with bisphosphonates. In addition to cross-sectional data, longitudinal data were available from 22 patients with an average follow-up period of 7.6 years. The patients, who had OI types I, III, IV, VI, and VII, had been treated with zoledronic acid, pamidronate, or risedronate for 3.2 years on average. RESULTS: Altogether 33% of the 39 bisphosphonate-treated patients had at least 1 cranial base anomaly, platybasia being the most prevalent diagnosis (28%). Logistic regression analysis suggested a higher risk of basilar impression or invagination in patients with severe OI (OR 22.04) and/or older age at initiation of bisphosphonate treatment (OR 1.45), whereas a decreased risk was associated with longer duration of treatment (OR 0.28). No significant associations between age, height, or cumulative bisphosphonate dose and the risk for cranial base anomaly were detected. In longitudinal evaluation, Kaplan-Meier curves suggested delayed development of cranial base pathology in patients treated with bisphosphonates but the differences from the untreated group were not statistically significant. CONCLUSIONS: These findings indicate that cranial base pathology may develop despite bisphosphonate treatment. Early initiation of bisphosphonate treatment may delay development of craniocervical junction pathology. Careful followup of cranial base morphology is warranted, particularly in patients with severe OI.

Zoledronic acid treatment in children with osteogenesis imperfecta.

BACKGROUND: Intravenous disodium pamidronate has become an established treatment in osteogenesis imperfecta (OI). Another bisphosphonate, zoledronic acid, has been indicated for the treatment of adult osteoporosis. We studied its efficacy and safety in children with mild OI. METHODS: Patients were treated for 1.0-3.2 years with 0.05 mg/kg zoledronic acid intravenously every 6 months as part of their clinical care. They were carefully followed for clinical and biochemical parameters, side effects, bone mineral densities (BMD) and compression fractures. RESULTS: The study included 17 patients (age 1.5-16.8 years) with type I OI. They had sustained altogether 73 fractures; 9 had compression fractures. During the treatment, 6 patients suffered in total 10 new long-bone fractures. The median lumbar spine areal BMD z-score increased from -2.0 to -0.7 during 2 years of treatment. The infusions were associated with a transient decrease in serum calcium and phosphate and a significant increase in serum PTH. Two patients developed symptomatic hypocalcemia. Bone turnover markers decreased during the treatment. CONCLUSIONS: Intravenous zoledronic acid is an effective mode of treatment in children with OI. The treatment response is comparable to pamidronate but the infusion protocol is more convenient. Further studies are needed to establish optimal dosing and long-term safety.