Approach to the Patient: Pharmacological Therapies for Fracture Risk Reduction in Adults With Osteogenesis Imperfecta

• Published in: The journal of clinical endocrinology and metabolism 2023-07, Vol.108 (7), p.1787-1796
• Main Authors: Liu, Winnie, Lee, Brendan, Nagamani, Sandesh C S, Nicol, Lindsey, Rauch, Frank, Rush, Eric T, Sutton, V Reid, Orwoll, Eric
• Format: Article
• Language: English
• Subjects: 17β-Estradiol; Adult; Adults; Antagonists; Bisphosphonates; Bone Density; Bone Density Conservation Agents - pharmacology; Bone Density Conservation Agents - therapeutic use; Bone diseases; Bone mineral density; Bones; Care and treatment; Clinical trials; Collagen; Collagen (type I); Database searching; Density; Development and progression; Diphosphonates - therapeutic use; Disodium pamidronate; Fracture Fixation - adverse effects; Fractures; Fractures, Bone - etiology; Fractures, Bone - prevention & control; Genetic disorders; Humans; Internet/Web search services; Online searching; Osteogenesis; Osteogenesis imperfecta; Osteogenesis Imperfecta - complications; Osteogenesis Imperfecta - drug therapy; Osteoporosis; Parathyroid hormone; Post-translation; Risk factors; SOST protein; Teriparatide - pharmacology; Teriparatide - therapeutic use; Testosterone
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/clinem/dgad035

Abstract Context Osteogenesis imperfecta (OI) is a genetic disorder characterized by increased bone fragility largely caused by defects in structure, synthesis, or post-translational processing of type I collagen. The effectiveness of medications used for fracture reduction in adults with OI is understudied and practice recommendations are not well established. Drugs currently used to improve skeletal health in OI were initially developed to treat osteoporosis. Oral and intravenous bisphosphonates have been shown to improve bone mineral density (BMD) in adults with OI and are commonly used; however, conclusive data confirming fracture protection are lacking. Similarly, teriparatide appears to increase BMD, an effect that seems to be limited to individuals with type I OI. The role of denosumab, abaloparatide, romosozumab, and estradiol/testosterone in adult OI have not been systematically studied. Anti-sclerostin agents and transforming growth factor-beta antagonists are under investigation in clinical trials. Objective This review summarizes current knowledge on pharmacologic treatment options for reducing fracture risk in adults with OI. Methods A PubMed online database search of all study types published in the English language using the terms “osteogenesis imperfecta,” “OI,” and “brittle bone disease” was performed in June 2022. Articles screened were restricted to adults. Additional sources were identified through manual searches of reference lists. Conclusion Fracture rates are elevated in adults with OI. Although clinical trial data are limited, bisphosphonates and teriparatide may be useful in improving BMD. Further research is needed to develop medications for adults with OI that will lead to definite fracture rate reduction.