Bone events and evolution of biologic markers in Gaucher disease before and during treatment.
BACKGROUND
Known biomarkers of Gaucher-disease activity are platelets, chitotriosidase, angiotensin-converting enzyme (ACE), tartrate-resistant acid phosphatase (TRAP) and ferritin. The aim of this study was to retrospectively evaluate the frequency of bone events (BE) and biomarker changes during two periods: diagnosis to first enzyme-replacement therapy (ERT) and the latter to the closing date.


METHODS
BE of 62 treated patients, among the 73-patient cohort followed at Beaujon Hospital, Clichy, France, were described with Kaplan-Meier curves, and linear-mixed models were used to analyze their biomarker changes and the influence of several covariates (splenectomy, diagnosis year, genotype, age at diagnosis and sex).


RESULTS
BE occurred before (54 events in 21 patients), but also during, ERT (12 events in 10 patients), with respective frequencies (95% confidence interval) at 10 years of 22.4% (13.3 to 36.3) and 20.0% (10.2 to 36.9). Biomarker slope changes before and during ERT differed significantly for platelets (+190/mm3/year and 7,035/mm3/year, respectively; P < 0.0001) and ferritin (+4% and -14%; P < 0.0001). High ferritin levels and low platelet counts at ERT onset were significantly associated with BE during ERT (P = 0.019 and 0.039, respectively). Covariates significantly influenced biomarker changes (baseline and/or slope): splenectomy affected platelets (baseline and changes), TRAP changes and chitotriosidase changes; diagnosis date influenced ACE and TRAP baseline values; and genotype influenced chitotriosidase baseline and changes.


CONCLUSIONS
Platelet counts and ferritin levels and their slope changes at ERT onset seem to predict BE during treatment. Biomarker baseline values and changes are dependent on several covariables.
Stirnemann
Jérôme
J
Hôpital Jean-Verdier, Assistance Publique-Hôpitaux de Paris, Université Paris XIII, 93140 Bondy Cedex, France. jerome.stirnemann@jvr.aphp.fr
Belmatoug
Nadia
N
Vincent
Corine
C
Fain
Olivier
O
Fantin
Bruno
B
Mentré
France
F
D000135:Acid Phosphatase / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism*; D001847:Bone Diseases / Q000453:epidemiology* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018450:Disease Progression; D056947:Enzyme Replacement Therapy; D005260:Female; D005293:Ferritins / Q000378:metabolism; D050723:Fractures, Bone / Q000453:epidemiology* / Q000378:metabolism; D005776:Gaucher Disease / Q000188:drug therapy / Q000453:epidemiology / Q000378:metabolism; D005962:Glucosylceramidase / Q000627:therapeutic use*; D006596:Hexosaminidases / Q000378:metabolism; D006801:Humans; D007223:Infant; D007527:Isoenzymes / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D010976:Platelet Count; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D000071681:Tartrate-Resistant Acid Phosphatase; D055815:Young Adult
D015415:Biomarkers; D007527:Isoenzymes; D005293:Ferritins; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D006596:Hexosaminidases; C086400:chitotriosidase; D005962:Glucosylceramidase; D007703:Peptidyl-Dipeptidase A