Effects of bisphosphonates in children with osteogenesis imperfecta: An AACPDM systematic review

Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Developmental Medicine & Child Neurology (Impact Factor: 3.29). 02/2009; 51(1):17-29. DOI: 10.1111/j.1469-8749.2008.03222.x
Source: PubMed

ABSTRACT This systematic review of the effects of bisphosphonate treatment in children with osteogenesis imperfecta was conducted using the American Academy for Cerebral Palsy and Developmental Medicine methodology for developing systematic reviews of treatment interventions (Revision 1.1) 2004. Despite a large body of published literature, there have been only eight studies with a sufficiently high level of internal validity to be truly informative. These studies confirm improvement in bone density. Many, but not all studies, demonstrate reduction in fracture rate and enhanced growth. There has been extremely limited evaluation of broader treatment impacts such as deformity, need for orthopedic surgery, pain, functioning, or quality of life. Short-term side effects were minimal. Which medication and dosing regimen is optimal and how long patients should be treated are unclear. This body of evidence would be strengthened by a larger controlled trial, because many studies lacked adequate power to evaluate stated outcomes. These studies do not address the impacts of bisphosphonates in children with milder forms of osteogenesis imperfecta and severe forms that are not due to mutations in the type I pro-collagen gene (e.g. types VII and VIII). Additional research is needed into treatment of infants. More studies evaluating medication choices, optimal dosing, duration of treatment, post-treatment impacts, and long-term side effects are necessary.

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    • "Such pharmacologic treatments are now commonly used on children (sometime extremely young) during long periods (2–5 years) with the rationale to maximize the impact on a growing skeleton. However, some concerns have been raised about the equivocal efficiency on the fracture reduction [4] [5], the accumulation of those long life drugs and the impact of inhibiting bone remodelling over long periods, which results in the build-up of poor quality, highly mineralized bone [1] [6]. It is recognized that the bone tissue is highly responsive to dynamic loading and is able to adapt its architecture and mass to the mechanical loading environment [7] [8] [9]. "
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    ABSTRACT: Osteogenesis imperfecta (OI) is characterized by extremely brittle bone. Currently, bisphosphonate drugs allow a decrease of fracture by inhibiting bone resorption and increasing bone mass but with possible long term side effects. Whole body mechanical vibrations (WBV) treatment may offer a promising route to stimulate bone formation in OI patients as it has exhibited health benefits on both muscle and bone mass in human and animal models. The present study has investigated the effects of WBV (45 Hz, 0.3 g, 15 minutes/days, 5 days/week) in young OI (oim) and wild type female mice from 3 to 8 weeks of age. Vibration therapy resulted in a significant increase in the cortical bone area and cortical thickness in the femur and tibia diaphysis of both vibrated oim and wild type mice compared to sham controls. Trabecular bone was not affected by vibration in the wild type mice; vibrated oim mice, however, exhibited significantly higher trabecular bone volume fraction in the proximal tibia. Femoral stiffness and yield load in three point bending were greater in the vibrated wild type mice than in sham controls, most likely attributed to the increase in femur cortical cross sectional area observed in the μCT morphology analyses. The vibrated oim mice showed a trend toward improved mechanical properties, but bending data had large standard deviations and there was no significant difference between vibrated and non-vibrated oim mice. No significant difference of the bone apposition was observed in the tibial metaphyseal trabecular bone for both the oim and wild type vibrated mice by histomorphometry analyses of calcein labels. At the mid diaphysis, the cortical bone apposition was not significantly influenced by the WBV treatment in both the endosteum and periosteum of the oim vibrated mice while a significant change is observed in the endosteum of the vibrated wild type mice. As only a weak impact in bone apposition between the vibrated and sham groups is observed in the histological sections, it is possible that WBV reduced bone resorption, resulting in a relative increase in cortical thickness. Whole body vibration appears as a potential effective and innocuous means for increasing bone formation and strength, which is particularly attractive for treating the growing skeleton of children suffering from brittle bone disease or low bone density pathologies without the long term disadvantages of current pharmacological therapies.
    Bone 01/2013; 53(2). DOI:10.1016/j.bone.2013.01.023 · 4.46 Impact Factor
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    ABSTRACT: In der Erwachsenenmedizin liegen zahlreiche klinische Studien vor, die die Wirkung von Bisphosphonaten als effektive Hemmer der Knochenresorption eindeutig belegen [17], [19], [21], [35]. Bisphosphonate sind im Erwachsenenalter hauptsächlich zur Behandlung der Osteoporose oder der tumorassoziierten Hyperkalziämie indikationsabhängig zugelassen [18], [20], [21]. Der erfolgreiche Einsatz von Bisphosphonaten beim Morbus Paget des Erwachsenen ist durch langjährige Erfahrungen belegt [40]. Anhand des aktuellen Wissensstandes scheinen Bisphosphonate in der Mehrzahl aller Osteopathien therapeutisch hilfreich zu sein.
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    ABSTRACT: Introduction/Aims: Osteogenesis imperfecta (OI) is a genetic disorder characterized by bone fragility and osteopenia. Treatment involves a multidisciplinary approach and aims to improve the quality of life. The authors aimed to describe the characteristics of a sample of children with OI, to evaluate the treatment and clinical outcome before and after therapy. Material and Methods: An observational, longitudinal, retrospective and analytic study based on data obtained from the analisys of the clinical files of all patients with OI included in the pamidronate treatment protocol in Dona Estefânia's Hospital. The studied variables were: gender, age at diagnosis, familiar history of OI, age at fracture, fracture location, number of fractures, medical/surgical therapy, age at onset of treatment, number of courses of medical therapy, age at surgical treatment and its complications. A five percent statistics significance level was adopted. Results: in 21 patients, 61.9% were male and 11 had its OI type registered (five type I, three type III, three type IV). The average age of diagnosis was 20.6 months and there were two diagnostic peaks: the first month - 37%, and 24 months - 26%. On average patients had 0.62 fractures/patient/year, of which 17.4% in the perinatal period and 62% before age three. Most of the fractures occurred in the lower limbs (55.6%). All patients underwent medical treatment, starting at an average of 4.3 years. In follow-up sample (n=14) there was a decrease in the number of fractures after starting treatment with pamidronate (0.76 to 0.35 fractures/patient/year). Intramedullary rods were placed in nine patients (64.3%). In eight patients they were placed in the femur, four unilateral and four bilateral, with no prior history of fracture in three cases. There were no new fractures in the surgically treated bones. Conclusion: OI is a disease with a wide clinical variability that mainly depends on its type. Despite no cure has been found, medical treatment with biphosphonates and surgical treatment, with intramedullary rods, seems to reduce the incidence of new fracture occurrence.
    Acta medica portuguesa 26(1):5-11. · 0.28 Impact Factor
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