Management of Osteogenesis Imperfecta

Abstract

Osteogenesis imperfecta (OI) is the term used to describe a group of rare inherited skeletal disorders characterized by a greatly increased risk of fragility fractures (1). Mutations in several genes can cause OI but the condition is most commonly caused by mutations of COLIA1 or COL1A2 resulting in the production of collagen which is abnormal or present in reduced amounts. Fractures in OI are particularly common during childhood but the elevated fracture risk continues throughout life. Bone mineral density (BMD) can be reduced in OI but the magnitude of increase in fracture risk is far greater than can be accounted for by low BMD, highlighting that a key mechanism of bone fragility is reduced bone quality due to defects of bone matrix and mineralization. A multidisciplinary approach is needed to optimize management of OI, with input from physicians, orthopedic surgeons, physiotherapists, occupational therapists, and other allied health professionals. Orthopedic surgery plays a key role both in the fixation of fractures and in the correction of limb deformities. Bisphosphonates have been widely used in the treatment of children and adults with OI. Although there is good evidence that they increase BMD, it is uncertain to what extent they reduce fracture risk. Clinical trials of bone anabolic drugs such as teriparatide and inhibitors of sclerostin have also been studied; although they increase BMD, studies of these agents have not been powered to look at fracture endpoints. Various other treatment modalities including denosumab, and cell therapy have been explored but haven't gained acceptance in routine clinical practice. There have been huge advances in understanding the pathogenesis of OI but these have not been accompanied by advances in treatment. This signals need for well-designed clinical trials with fracture endpoints in OI, both with existing agents and with the newer therapeutic agents that are now starting to emerge.

Case Report: Hyperplastic Callus of the Femur Mimicking Osteosarcoma in Osteogenesis Imperfecta Type V

“…Randomized controlled trials of bisphosphonates in OI have consistently shown that BMD is increased, but the effects of bisphosphonates on fracture rate are uncertain (11). As to our patient, he had no more fractures after 6 years' administration of bisphosphonate, and his bone density increased, his Z-score was above −2.0; meanwhile, considering the drug holiday of bisphosphonates, we didn't administrate bisphosphonates at the latest admission.…”

Mechanisms of Bone Fragility: From Osteogenesis Imperfecta to Secondary Osteoporosis

“…Notably, RANKL promotes osteoclast differentiation (see Section 2.4 ). At present, denosumab, a monoclonal antibody against RANKL, which inhibits osteoclastic activity, is being tested in clinical trials in OI patients [ 42 ].…”

Osteogenesis imperfecta and physical therapy: A review of recent trends during the COVID-19 pandemic

“…Bisphosphonates are commonly used. These drugs 189 have anti-resorptive properties which inhibit the function of osteoclasts (Ralston and Gaston, 2020) . Treatment with cyclical intravenous pamidronate, a second-generation bisphosphonate, has shown better results in children.…”

“…However, the death rate may be higher than expected in children as they are prone to infection due to low immunity (Fauci et al, 2020). The best treatment practice is multi-disciplinary approach (Mueller et al, 2018;Ralston and Gaston, 2020). This review aims to identify the potential effects of the multidisciplinary approach in patients with orthopaedic conditions.…”