Low bone density and bone metabolism alterations in Duchenne muscular dystrophy: response to calcium and vitamin D treatment.
Boys with Duchenne muscular dystrophy often have reduced bone mass and increased fracture risk. In this prospective study on 33 patients, calcifediol (25-OH vitamin D(3)) plus adjustment of dietary calcium to the recommended dose reduced bone resorption, corrected vitamin D deficiency, and increased bone mass in about two-thirds of cases.


BACKGROUND
Low BMC and BMD and bone metabolism alterations are frequent in boys with Duchenne muscular dystrophy (DMD), especially now that long-term glucocorticosteroid (GC) treatment is the standard of care. This prospective study was designed to evaluate the effects of a first-line treatment (25-OH vitamin D(3) [calcifediol] plus adjustment of dietary calcium to the recommended daily dose) on bone.


METHODS
Thirty-three children with DMD on GC treatment were followed for 3 years: one of observation and two of treatment.


RESULTS
spine and total body BMC and BMD increase; secondary outcome: changes in bone turnover markers (C-terminal [CTx] and N-terminal [NTx] telopeptides of procollagen type I; osteocalcin [OC]).


RESULTS
During the observation year, BMC and BMD decreased in all patients. At baseline and after 12 months, serum CTx and urinary NTx were higher than normal; OC and parathyroid hormone at the upper limit of normal; 25-OH vitamin D(3) significantly lower than normal. After 2 years of calcifediol and calcium-rich diet, BMC and BMD significantly increased in over 65% of patients, and bone metabolism parameters and turnover markers normalized in most patients (78.8%). During the observation year, there were four fractures in four patients, while during the 2 years of treatment there were two fractures in two patients.


CONCLUSIONS
Calcifediol plus adequate dietary calcium intake seems to be an effective first-line approach that controls bone turnover, corrects vitamin D deficiency, and increases BMC and BMD in most patients with DMD. Lack of response seems related to persistently high bone turnover.
Bianchi
M L
ML
Centro Malattie Metaboliche Ossee, Istituto Auxologico Italiano IRCCS, Milan, Italy. ml.bianchi@auxologico.it
Morandi
L
L
Andreucci
E
E
Vai
S
S
Frasunkiewicz
J
J
Cottafava
R
R
D000293:Adolescent; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016723:Bone Remodeling / Q000187:drug effects*; D001862:Bone Resorption / Q000188:drug therapy; D002112:Calcifediol / Q000008:administration & dosage / Q000494:pharmacology*; D002136:Calcium, Dietary / Q000008:administration & dosage / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D024042:Collagen Type I / Q000378:metabolism; D005938:Glucocorticoids / Q000009:adverse effects; D006801:Humans; D008297:Male; D020388:Muscular Dystrophy, Duchenne / Q000150:complications* / Q000188:drug therapy; D015675:Osteocalcin / Q000097:blood; D010281:Parathyroid Hormone / Q000097:blood; D010455:Peptides / Q000378:metabolism; D011446:Prospective Studies; D016896:Treatment Outcome; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D014808:Vitamin D Deficiency / Q000188:drug therapy
D050071:Bone Density Conservation Agents; D002136:Calcium, Dietary; D024042:Collagen Type I; D005938:Glucocorticoids; D010281:Parathyroid Hormone; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D002112:Calcifediol
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