title: Long-term bone density evaluation in cerebrotendinous xanthomatosis: evidence of improvement after chenodeoxycholic acid treatment.
abstract: Cerebrotendinous xanthomatosis (CTX) is known to be associated with osteoporosis and a higher incidence of bone fractures. However, the underlying pathogenesis is still unknown, and the effects of long-term replacement therapy with chenodeoxycholic acid (CDCA) on bone mineral density (BMD) have not been fully investigated. We studied 11 CTX patients aged 13-43 years. We performed dual-energy X-ray absorptiometry and assessed serum cholestanol and 25-hydroxyvitamin D (25-OHD) concentrations both at the time of diagnosis and after long-term treatment with CDCA. At baseline, we found low BMD in nine patients, cholestanol elevation in all subjects, and 25-OHD decrease in nine. After a mean follow-up time of 30 months (range 24-36), no substantial clinical changes including bone fractures occurred; and we detected a significant increase of both planar and volumetric BMD as well as normalization of plasma cholestanol levels and increase of serum 25-OHD. Densitometric improvement following CDCA introduction was not correlated to changes of biochemical parameters. Our study confirms the presence of low bone mass in CTX and demonstrates that long-term CDCA treatment increases bone mineral content. In this respect, improvement of vitamin D intestinal absorption secondary to bile acid restoration could play an important role. Moreover, our data strongly suggest the utility of periodic bone density evaluation in CTX patients.
authors.affiliation: Department of Internal Medicine, Endocrine-Metabolic Sciences and Biochemistry, University of Siena, Siena, Italy. martinig@unisi.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Martini
authors.forename: Andrea
authors.initials: A
authors.lastname: Mignarri
authors.forename: Martina
authors.initials: M
authors.lastname: Ruvio
authors.forename: Roberto
authors.initials: R
authors.lastname: Valenti
authors.forename: Beatrice
authors.initials: B
authors.lastname: Franci
authors.forename: Marina
authors.initials: M
authors.lastname: Del Puppo
authors.forename: Antonio
authors.initials: A
authors.lastname: Federico
authors.forename: Ranuccio
authors.initials: R
authors.lastname: Nuti
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Dotti
mesh_terms: D015502:Absorptiometry, Photon; D000293:Adolescent; D000328:Adult; D015519:Bone Density; D002635:Chenodeoxycholic Acid / Q000627:therapeutic use*; D004083:Cholestanol / Q000097:blood; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D010024:Osteoporosis / Q000209:etiology; D013995:Time; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D019294:Xanthomatosis, Cerebrotendinous / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D005765:Gastrointestinal Agents; D002635:Chenodeoxycholic Acid; D014807:Vitamin D; D004083:Cholestanol; C104450:25-hydroxyvitamin D