Treatment of Osteogenesis Imperfecta: Who, Why, What?

Abstract

Introduction: Osteogenesis imperfecta (OI) is a heritable disorder characterized by bone fragility and reduced bone mass. It may present with a wide range of severity. About 85% of the cases are linked to mutations in one of the two genes encoding type I collagen. In other cases of OI, there are mutations in the expression of a cartilage-related protein or of 3-prolyl-hydroxylase.Increased bone turnover rate, due to the repair activity triggered to replace weak tissue, is the rule. Often, disuse bone loss further compounds the decrease in bone mass. These findings justify the use of bisphosphonates to reduce osteoclast-mediated bone resorption, and so tilt the remodeling balance towards an increase in bone mass. Conclusions: Cyclical intravenous pamidronate administration reduces bone pain, and increases bone mass and density. No negative effects on growth or fracture repair have been observed. There is an increase in size of vertebral bodies and thickening of cortical bone, which translates into decreased fracture incidence and improved ambulation. However, the long-term consequences of low bone turnover in children with OI are unknown at the present time. Innovative surgery and specific occupational and physiotherapy programs are integral parts of the treatment protocol. This approach will prevail until gene-based therapies become clinically applicable.

Pamidronate Affects the Mandibular Cortex of Children with Osteogenesis Imperfecta

“…Multidisciplinary OI treatment aims to prevent bone deformities and maximize functional capabilities (Glorieux 2007). Intravenous pamidronate treatment (PAM), which inhibits the function of osteoclasts, has shown to increase bone mineral density (BMD), reduce bone pain, decrease fracture rate, and improve growth, muscle strength, and mobility in patients since birth (Zeitlin et al 2003;Kusumi et al 2014).…”

Current and emerging treatments for the management of osteogenesis imperfecta

“…[17][18][19] For simplicity, the objectives of treatment can be reduced to three typical situations (Table 1): the mild form (type I), in which the aim is to reach 'normal life'; the severe and moderate forms (types III-IX), in which the objective is 'autonomy'; and the lethal perinatal form (type II), in which the problem is survival at birth.…”

Avaliação da qualidade óssea mandibular em crianças com osteogênese imperfeita em uso de pamidronato

“…Essas crianças têm menos a ganhar porque seu status funcional é melhor mesmo sem tratamento, assim, até o momento é recomendado que elas não sejam tratadas com fármacos. Cirurgias ortopédicas, programas de fisioterapia e reabilitação são partes integrais do protocolo de tratamento, e essa abordagem deve prevalecer até que as terapias genéticas tornem-se clinicamente aplicáveis (Glorieux, 2007).…”

“…Sillence, 2014). Essas mutações podem causar a redução da síntese e da secreção do colágeno tipo I, além disso, há o aumento da taxa de remodelação óssea devido à atividade reparadora para substituição do tecido ósseo enfraquecido (Glorieux, 2007). A produção diminuída do colágeno tipo I com estrutura molecular normal geralmente leva à osteogênese imperfeita tipo I, mais branda e com ausência de grandes deformidades.…”

“…Também tem sido notado um aumento na espessura da cortical, no número de trabéculas e na massa óssea das diáfises de ossos longos. Não têm sido observados efeitos negativos no crescimento nem em reparação de fraturas (Rauch e Glorieux, 2004;Rauch et al, 2006;Vallo et al, 2006;Glorieux, 2007Glorieux, e 2008.…”