title: Low bone mineral density is a common feature of Zellweger spectrum disorders.
abstract: Patients with Zellweger Spectrum Disorders (ZSDs) have impaired peroxisome biogenesis and severe, multisystem disease. Although the neurologic symptoms of ZSD tend to be the most prominent, patients also have hepatic, renal and adrenal impairment. Little is known about bone health in patients with ZSD, particularly those with mild or moderate presentation. We investigated 13 ZSD patients who had strikingly abnormal bone mineral density for age. DXA scans showed mean lumbar and femoral neck Z-scores of -3.2. There were no major differences between ambulatory and nonambulatory patients, and no biochemical abnormalities consistent with rickets or vitamin D deficiency were seen. Cyclic bisphosphonate therapy in one ZSD patient was successfully used to increase in bone mineral density. Although the etiology of bone disease in this condition is unknown, we speculate that altered signaling through the PPARγ pathway or deficient plasmalogens in patients with ZSD disrupts osteogenesis, resulting in poor bone formation and poor mineralization. Further investigation into the pathogenic mechanisms of bone disease in ZSD and the role of peroxisomal metabolism in osteogenesis may yield insights into the pathology of bone disease and suggest novel treatment options.
authors.affiliation: Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE, USA; Departments of Internal Medicine and Orthopaedic Surgery, University of Nebraska Medical Center, Omaha, NE, USA; Children's Hospital and Medical Center, Omaha, NE, USA. Electronic address: erush@unmc.edu.
authors.forename: Eric T
authors.initials: ET
authors.lastname: Rush
authors.affiliation: Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Goodwin
authors.affiliation: Departments of Human Genetics and Pediatrics, McGill University, Montreal, QC, Canada.
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Braverman
authors.affiliation: Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE, USA; Children's Hospital and Medical Center, Omaha, NE, USA.
authors.forename: William B
authors.initials: WB
authors.lastname: Rizzo
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D015502:Absorptiometry, Photon; D000293:Adolescent; D015519:Bone Density / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D005272:Femur Neck; D006801:Humans; D007223:Infant; D008161:Lumbosacral Region; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D010012:Osteogenesis; D047495:PPAR gamma / Q000378:metabolism*; D020675:Peroxisomes / Q000378:metabolism; D014807:Vitamin D / Q000097:blood; D015211:Zellweger Syndrome / Q000235:genetics / Q000503:physiopathology*
chemical_list: D050071:Bone Density Conservation Agents; D008565:Membrane Proteins; D047495:PPAR gamma; D014807:Vitamin D; D000074183:ATPases Associated with Diverse Cellular Activities; C111808:PEX1 protein, human
keywords: Bisphosphonate; Bone densitometry; Bone mineral density; PPAR-gamma; Pathologic fracture; Peroxisomal biogenesis disorder; Zellweger spectrum disorder