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

Abstract

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.

Osteogenesis Imperfecta: New Perspectives From Clinical and Translational Research

“…We found that about 25% of fractures occurring in the nondeformed femurs of individuals with OI fulfill the criteria of atypical femur fractures, regardless of whether they had been exposed to bisphosphonates . Overall, systematic studies on more than 300 femur fractures have failed to detect a relationship between bisphosphonate use and diaphyseal femur fractures in OI . These studies concurred that the main risk factor for such femur fractures in OI was the severity of the underlying disease rather than bisphosphonate treatment history.…”

“…(42) Overall, systematic studies on more than 300 femur fractures have failed to detect a relationship between bisphosphonate use and diaphyseal femur fractures in OI. (42)(43)(44) These studies concurred that the main risk factor for such femur fractures in OI was the severity of the underlying disease rather than bisphosphonate treatment history. We submit that labeling diaphyseal femur fractures that are common in OI as "atypical" because they are rare in the context of postmenopausal osteoporosis is confusing and should be avoided.…”

Challenges of delivery of dental care and dental pathologies in children and young people with osteogenesis imperfecta

“…Previous concerns were that bisphosphonates may affect dental development through reduced resorption of deciduous dentition roots and surrounding bone delaying permanent dentition eruption (Bhatt et al 2014). Animal studies indicated delayed dental development (Bradaschia-Correa et al 2007), whereas recent paediatric OI data are reassuring that bisphosphonate treatment normalises rate of dental development in OI (Vuorimies et al 2017). Bisphosphonates may complicate orthodontic treatment through osteoclast inhibition decreasing tooth movement lengthening treatment time (Iglesias-Linares et al 2010).…”

Pamidronate decreases bilirubin-impaired cell death and improves dentinogenic dysfunction of stem cells from human deciduous teeth

“…Indeed, pamidronate is used as safety medicine to reduce bone fracture in pediatric patients with osteogenesis imperfecta (OI) [ 41 ]. OI patients with pamidronate treatment show a delaying dental eruption in comparison with OI patients with naïve treatment, but not indistinguishable from normal ones [ 42 ]. Further studies will be necessary to understand the effects of pamidronate alone on cell functions including cell apoptosis and odontogenesis and the related intracellular signal transduction in SHED for pediatric patients receiving pamidronate.…”