The clinical spectrum and pathophysiology of skeletal complications in lysosomal storage disorders

• Published in: Baillière's best practice & research. Clinical endocrinology & metabolism Vol. 29; no. 2; pp. 219 - 235
• Main Authors: Clarke, Lorne A., MDCM, FRCPC, FCCMG, Hollak, Carla E.M., MD, PhD
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.03.2015
• Subjects: Bone and Bones - metabolism; bone crisis; bone involvement; Cartilage - metabolism; dysosotosis multiplex; Dysostoses - etiology; Dysostoses - metabolism; Dysostoses - therapy; Endocrinology & Metabolism; Enzyme Replacement Therapy; Gaucher disease; Hematopoietic Stem Cell Transplantation; Humans; Lysosomal Storage Diseases - complications; Lysosomal Storage Diseases - metabolism; Lysosomal Storage Diseases - therapy; lysosomal storage disorders; mucolipidosis; mucopolysaccharidosis; osteonecrosis; Osteonecrosis - etiology; Osteonecrosis - metabolism; Osteonecrosis - therapy; osteoporosis; Osteoporosis - etiology; Osteoporosis - metabolism; Osteoporosis - therapy; pycnodysostosis; Pycnodysostosis - etiology; Pycnodysostosis - metabolism; Pycnodysostosis - therapy; mucolipidosis; dysosotosis multiplex; Gaucher disease; lysosomal storage disorders; mucopolysaccharidosis; bone involvement; osteonecrosis; osteoporosis; bone crisis; pycnodysostosis
• ISSN: 1521-690X; 1878-1594
• DOI: 10.1016/j.beem.2014.08.010

Lysosomal storage disorders affect multiple organs including the skeleton. Disorders with prominent skeletal symptoms are type 1 and 3 Gaucher disease, the mucopolysaccharidoses, the glycoproteinoses and pycnodysostosis. Clinical manifestations range from asymptomatic radiographical evidence of bone pathology to overt bone crises (Gaucher), short stature with typical imaging features known as dysostosis multiplex (MPS), with spine and joint deformities (mucopolysaccharidoses, mucolipidosis), or osteopetrosis with pathological fractures (pynodysostosis). The pathophysiology of skeletal disease is only partially understood and involves direct substrate storage, inflammation and other complex alterations of cartilage and bone metabolism. Current treatments are enzyme replacement therapy, substrate reduction therapy and hematopoietic stem cell transplantation. However, effects of these interventions on skeletal disease manifestations are less well established and outcomes are highly dependent on disease burden at treatment initiation. It is now clear that adjunctive treatments that target skeletal disease are needed and should be part of future research agenda.